ANTI-IGE ANTIBODIES

Abstract

This application concerns a set of anti-IgE antibodies to a novel region of Cε (β5-helix region of Cε2) and their use in the blocking of IgE to Fcε receptors (FcεRI and CD23) for the treatment of diseases mediated by IgE such as allergic airway diseases including asthma. Of note, these anti-IgE antibodies not only bind but also remove pre-bound IgE from Fcε receptors.

Description

BACKGROUND OF THE INVENTION

Immunoglobulin E (IgE) is a sensor molecule that plays a pivotal role in inducing the immediate reaction. IgE binds its high affinity receptor FcεRI and confers a versatile recognizing ability to mast cell and basophils, which are the main effector cells in the immediate allergic reaction. Upon binding of allergens, mast cells and basophils are quickly activated, and they release a wide variety of inflammation mediator molecules including histamine, proteases, lipid mediators, cytokines, and chemokines.

This application contains a sequence listing which is electronically filed concurrently herewith as 119897-0004UT01, file size 448 KB with a production date of Feb. 8, 2024, which is incorporated by reference herein.

SUMMARY OF THE INVENTION

According to one aspect of the disclosure, an antigen binding polypeptide is provided wherein the polypeptide exhibits specific binding to an IgE.

In some embodiments, the binding of the antigen binding polypeptide to the IgE disrupts interaction between the IgE and at least one Fcε receptor.

In some embodiments, the disrupted interaction comprises blocking an unbound IgE from binding to the at least one Fcε receptor. In some embodiments, the disrupted interaction comprises dissociating a bound IgE from the at least one Fcε receptor.

In some embodiments, the disrupted interaction results in suppression of degranulation.

In some embodiments, the at least one Fcε receptor comprises FcεRI. In some embodiments, the at least one Fcε receptor comprises CD23. In some embodiments, the at least one Fcε receptor comprises FcεRI and CD23.

In some embodiments, the antigen binding polypeptide specifically binds to at least one amino acid residue in β5-helix region of the Cε2, wherein the β5-helix region is the combination of helix, β5-helix joint, and lower half of β5 that connects to helix of Cε2.

In some embodiments, the antigen binding polypeptide specifically binds to at least one amino acid residue in the helix of Cε2. In some embodiments, the antigen binding polypeptide specifically binds to at least one amino acid residue in the β5-helix joint of Cε2. In some embodiments, the antigen binding polypeptide specifically binds to at least one amino acid residue in the lower half of β5 that connects to helix of Cε2.

In some embodiments, the antigen binding polypeptide does not bind to amino acid residue T298 of Cε2.

In some embodiments, the antigen binding polypeptide binds to at least two amino acid residues in the β5-Cε2 helix region.

In some embodiments, the antigen binding polypeptide does not bind to β3 region of Cε2. In some embodiments, the antigen binding polypeptide does not bind to β4 region of Cε2. In some embodiments, the antigen binding polypeptide does not bind to β3 or β4 region of Cε2.

In some embodiments, the antigen binding polypeptide comprises at least one amino acid sequence selected from SEQ ID Nos 1-25. In some embodiments, the antigen binding polypeptide comprises at least one amino acid sequence selected from SEQ ID Nos 26-50.

In some embodiments, the antigen binding polypeptide comprises at least one amino acid sequence selected from SEQ ID Nos 51-200.

According to another aspect of the disclosure, an antibody or a fragment thereof is provided. In some embodiments, the antibody or fragment has a Fab region that specifically binds to an IgE.

In some embodiments, the binding of the Fab to the IgE disrupts interaction between the IgE and at least one Fe receptor.

In some embodiments, the disrupted interaction comprises blocking an unbound IgE from binding to the at least one Fe receptor. In some embodiments, the disrupted interaction comprises dissociating a bound IgE from the at least one Fe receptor.

In some embodiments, the disrupted interaction results in suppression of degranulation.

In some embodiments, the at least one Fe receptor comprises FcεRI. In some embodiments, the at least one Fe receptor comprises CD23. In some embodiments, the at least one Fe receptor comprises FcεRI and CD23.

In some embodiments, the Fab region specifically binds to at least one amino acid residue in β5-helix region of the Cε2, wherein the β5-helix region is the combination of helix, β5-helix joint, and lower half of β5 that connects to helix of Cε2.

In some embodiments, the Fab region specifically binds to at least one amino acid residue in the helix of Cε2. In some embodiments, the Fab region specifically binds to at least one amino acid residue in the β5-helix joint of Cε2. In some embodiments, the Fab region specifically binds to at least one amino acid residue in the lower half of β5 that connects to helix of Cε2.

In some embodiments, the Fab region does not bind to amino acid residue T298 of Cε2.

In some embodiments, the Fab region binds to at least two amino acid residues in the β5-Cε2 helix region.

In some embodiments, the Fab region does not bind to β3 region of Cε2. In some embodiments, the Fab region does not bind to β4 region of Cε2. In some embodiments, the Fab region does not bind to β3 or β4 region of Cε2.

In some embodiments, the antibody is a bispecific antibody or a binding fragment thereof.

In some embodiments, the antibody comprises a monovalent Fab′, a divalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or binding fragment thereof.

In some embodiments, the Fab region comprises at least one heavy chain sequence selected from SEQ ID Nos 1-25. In some embodiments, the Fab region comprises at least one light chain sequence selected from SEQ ID Nos 26-50. In some embodiments, the Fab region comprises at least one complementarity determining region (CDR) selected from SEQ ID Nos 51-150, DAS, DVS, LSS, KAS, GAS, RAS, TTS, EAS, KTS, and SEQ ID Nos 176-200.

In some embodiments, the antibody exhibits a KD of less than 1 nM, 1.2 nM, 2 nM, 5 nM, 10 nM, 13.5 nM, 15 nM, 20 nM, 25 nM, or 30 nM.

In some embodiments, the antibody comprises a humanized antibody.

According to another aspect of the disclosure, an antibody or a fragment thereof having Fab region comprising specific heavy chain sequence, light chain sequence and/or CDR sequence is provided.

In some embodiments, the Fab region comprises at least one heavy chain sequence selected from SEQ ID Nos 1-25. In some embodiments, the Fab region comprises at least one light chain sequence selected from SEQ ID Nos 26-50. In some embodiments, the Fab region comprises at least one heavy chain sequence selected from SEQ ID Nos 1-25 and at least one light chain sequence selected from SEQ ID Nos 26-50.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 1 and a light chain sequence of SEQ ID No 26.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 2 and a light chain sequence of SEQ ID No 27.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 3 and a light chain sequence of SEQ ID No 28.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 4 and a light chain sequence of SEQ ID No 29.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 5 and a light chain sequence of SEQ ID No 30.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 6 and a light chain sequence of SEQ ID No 31.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 7 and a light chain sequence of SEQ ID No 32.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 8 and a light chain sequence of SEQ ID No 33.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 9 and a light chain sequence of SEQ ID No 34.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 10 and a light chain sequence of SEQ ID No 35.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 11 and a light chain sequence of SEQ ID No 36.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 12 and a light chain sequence of SEQ ID No 37.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 13 and a light chain sequence of SEQ ID No 38.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 14 and a light chain sequence of SEQ ID No 39.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 15 and a light chain sequence of SEQ ID No 40.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 16 and a light chain sequence of SEQ ID No 41.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 17 and a light chain sequence of SEQ ID No 42.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 18 and a light chain sequence of SEQ ID No 43.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 19 and a light chain sequence of SEQ ID No 44.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 20 and a light chain sequence of SEQ ID No 45.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 21 and a light chain sequence of SEQ ID No 46.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 22 and a light chain sequence of SEQ ID No 47.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 23 and a light chain sequence of SEQ ID No 48.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 24 and a light chain sequence of SEQ ID No 49.

In some embodiments, the Fab region comprises a heavy chain sequence of SEQ ID No 25 and a light chain sequence of SEQ ID No 50.

In some embodiments, the Fab region comprises an HCDR1 selected from SEQ ID Nos 51-75.

In some embodiments, the Fab region comprises an HCDR2 selected from SEQ ID Nos 76-100.

In some embodiments, the Fab region comprises an HCDR3 selected from SEQ ID Nos 101-125.

In some embodiments, the Fab region comprises an LCDR1 selected from SEQ ID Nos 126-150.

In some embodiments, the Fab region comprises an LCDR2 selected from SEQ ID Nos 151-175.

In some embodiments, the Fab region comprises an LCDR3 selected from SEQ ID Nos 176-200.

In some embodiments, the antibody exhibits a KD of less than 1 nM, 1.2 nM, 2 nM, 5 nM, 10 nM, 13.5 nM, 15 nM, 20 nM, 25 nM, or 30 nM.

In some embodiments, the antibody comprises a humanized antibody. In some embodiments, the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201-202. In some embodiments, the humanized antibody comprises a light chain variable region selected from SEQ ID Nos 203-206. In some embodiments, the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201-202, and a light chain variable region selected from SEQ ID Nos 203-206.

In some embodiments, the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201, and a light chain variable region selected from SEQ ID Nos 203-204. In some embodiments, the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 202, and a light chain variable region selected from SEQ ID Nos 205-206.

In some embodiments, the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207-208. In some embodiments, the humanized antibody comprises a light chain full sequence selected from SEQ ID Nos 209-212. In some embodiments, rein the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207-208, and a light chain variable region selected from SEQ ID Nos 209-212.

In some embodiments, the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207, and a light chain variable region selected from SEQ ID Nos 209-210. In some embodiments, the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 208, and a light chain variable region selected from SEQ ID Nos 211-212.

According to another aspect of the disclosure, a complex comprising the disclosed antigen binding polypeptide or the disclosed antibody or fragment is provided, wherein the complex comprises the polypeptide or antibody bound to IgE protein.

According to another aspect of the disclosure, a method is provided to disrupt an interaction between IgE and at least one Fe receptor by contacting a cell expressing the at least one Fe receptor with an antigen binding polypeptide that specifically binds to β5-helix region of the Cε2, wherein the β5-helix region is the combination of helix, β5-helix joint, and lower half of β5 that connects to helix of Cε2.

In some embodiments, the antigen binding polypeptide specifically binds to at least one amino acid residue in the helix of Cε2. In some embodiments, the antigen binding polypeptide specifically binds to at least one amino acid residue in the β5-helix joint of Cε2. In some embodiments, the antigen binding polypeptide specifically binds to at least one amino acid residue in the lower half of β5 that connects to helix of Cε2.

In some embodiments, the disrupted interaction comprises blocking an unbound IgE from binding to the at least one Fe receptor. In some embodiments, the disrupted interaction comprises dissociating a bound IgE from the at least one Fe receptor.

In some embodiments, the disrupted interaction results in suppression of degranulation.

In some embodiments, the at least one Fe receptor comprises FcεRI. In some embodiments, the at least one Fe receptor comprises CD23. In some embodiments, the at least one Fe receptor comprises FcεRI and CD23.

In some embodiments, the Fab region does not bind to amino acid residue T298 of Cε2.

In some embodiments, the Fab region binds to at least two amino acid residues in the β5-Cε2 helix region.

In some embodiments, the antigen binding polypeptide does not bind to β3 region of Cε2. In some embodiments, the antigen binding polypeptide does not bind to β4 region of Cε2. In some embodiments, the antigen binding polypeptide does not bind to β3 or β4 region of Cε2.

In some embodiments, the antigen binding polypeptide is an antibody or a binding fragment thereof. In some embodiments, the antibody comprises a monovalent Fab′, a divalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or binding fragment thereof.

In some embodiments, the Fab region comprises at least one heavy chain sequence selected from SEQ ID Nos 1-25.

In some embodiments, the Fab region comprises at least one light chain sequence selected from SEQ ID Nos 26-50.

In some embodiments, the Fab region comprises at least one complementarity determining region (CDR) selected from SEQ ID Nos 51-150, DAS, DVS, LSS, KAS, GAS, RAS, TTS, EAS, KTS, and SEQ ID Nos 176-200.

In some embodiments, the antibody exhibits a KD of less than 1 nM, 1.2 nM, 2 nM, 5 nM, 10 nM, 13.5 nM, 15 nM, 20 nM, 25 nM, or 30 nM.

In some embodiments, the antibody comprises a humanized antibody.

In some embodiments, the interaction between IgE and at least one Fcε receptor is associated with an allergic condition.

In some embodiments, the allergic condition is selected from asthma, chronic idiopathic urticaria, nasal polyps, hay fever, or food allergy.

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of the disclosure are set forth with particularity in the appended claims. The file of this patent contains at least one drawing/photograph executed in color. Copies of this patent with color drawing(s)/photograph(s) will be provided by the Office upon request and payment of the necessary fee. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which:

FIG. 1 illustrates binding of IgE to its high affinity receptor FcεRI according to some aspect of the disclosure, particularly showing the role of Cε2 and Cε3.

FIG. 2 illustrates a production process for an anti-human IgE Fab library according to some aspect of the disclosure.

FIG. 3 illustrates competition and removal assays according to some aspect of the disclosure.

FIG. 4 illustrates binding of selected Fabs tested in an ELISA according to some aspect of the disclosure. The purified Fabs were serially diluted and tested against a recombinant Cε2-4 protein coated at 2 μg/mL.

FIG. 5 illustrates blocking activities of the selected Fabs tested by flow cytometry according to some aspect of the disclosure. 0.5 μg/mL of IgE was incubated with different molar ratios of the Fabs and IgG at 37° C. for 1 h. The BaF/3 cell line transduced with human FcεRIα, β, and γ chains (BaF3-hFcεRI) was incubated with the Fab-treated IgE at 37° C. for 2 h. The binding of IgE to the cells was assessed as the binding capacity of the fluorescently labeled antigens.

FIG. 6 illustrates removal of the human IgEs on human FcεRIα-expressing mouse bone marrow-derived mast cells (BMMCs-hFcεRI) (A) and suppression of antigen-induced degranulation (B) according to some aspect of the disclosure. BMMCs-hFcεRI were incubated with 0.5 μg/mL of human IgE overnight. After washes, the cells were incubated with various concentrations of indicated Fab for 48 h. After washes, the cells were splitted into two experiments. In one experiment, the cells were incubated with fluorescently labeled antigens on ice, and the fluorescence levels, which represent the IgE amount on the cells, were measured by flow cytometry (A). In the other experiment, the cells were stimulated with antigens in the presence of anti-human CD63 antibodies, and the CD63 positive cells were considered as degranulating cells (B). Conc, concentration; MFI, mean fluorescence intensity.

FIG. 7 illustrates the competition (A) and removal (B) activities on IgE binding to human CD23 (hCD23) according to some aspect of the disclosure. (A) 2 μg/mL of IgE was incubated with 40 μg/mL of the indicated Fabs at 37° C. for 1 h. BaF/3 cell line transduced with human CD23 (BaF3-hCD23) was incubated with the Fab-treated IgE for 2 h on ice. After washes, the cells were incubated with fluorescently labeled antigens on ice, and the fluorescence was measured by flow cytometry. The MFIs were normalized to that of the cells incubated with non-treated IgE. (B) BaF-hCD23 cells were incubated with 2 μg/mL of human IgE overnight. After washes, the cells were incubated with 10 μg/mL of indicated Fab or omalizumab (Xolair) at 37° C. for 1 h. After washes, the cells were incubated with the fluorescently labeled antigen and the fluorescence levels were measured by flow cytometry. For Xolair, the same mass and molecular (mol) concentrations were used for comparison.

FIG. 8 illustrates the binding region of the three Fabs assessed by ELISA according to some aspect of the disclosure. (A,B) Recombinant his-tagged Cε2 protein fragment was treated with PNGaseF under the denaturing (A) or native (B) conditions. The Cε2 preparations were coated onto a microplate, and the binding of Fabs was assessed. (C) Human or mouse IgEs were coated on a microplate and detected by indicated Fabs or antibodies by ELISA. (D) The schematic representation of the Cε2 fragment of human IgE. Cε2 consists of seven β-sheets (numbered), one α-helix, and joining hinges. (E) Recombinant Cε2 mutants with human to mouse replacement in indicated regions were coated on a microplate. The binding of indicated Fabs and IgGs were assessed by ELISA. The readings were normalized to those of the anti-human IgE polyclonal antibody.

FIG. 9 illustrates the binding amino acids of the three Fabs in β5-Helix region assessed by ELISA according to some aspect of the disclosure. (A) Amino acid sequences of human and mouse Cε2 β5-Helix region. Gray-boxed amino acids are common for human and mouse IgE. Orange-underlined amino acids were replaced with those of mouse IgE in the indicated mutant IgE. (B) The wild-type (WT) and mutant chimera IgEs with the indicated regions of human to mouse replacements were coated onto a microplate. The binding levels of Fabs and anti-human IgE antibody were assessed by ELISA.

FIG. 10 illustrates the binding and stability of the mutant IgEs on the cell surface FcεRI assessed by flow cytometry according to some aspect of the disclosure. BaF3-hFcεRI cells were incubated with indicated human IgE mutants overnight. After washes, the cells were settled on ice for indicated time (A, 0 h; B, 3 h; C, 6 h). After washes, the cells were incubated with indicated concentrations of fluorescently labeled antigens on ice and subjected to the flow cytometry.

FIG. 11 illustrates the competitive activities of the three Fabs on the mutated IgEs assessed by flow cytometry according to some aspect of the disclosure. The human IgE mutants were incubated with the indicated Fabs or IgGs at 37° C. for 1 h. The BaF3-hFcεRI cells were incubated with the pretreated IgE mutants at 37° C. for 2 h. The binding of IgEs was assessed by the fluorescent antigen binding.

FIG. 12 illustrates the removal activities of the three Fabs (A) or the IgGs having the Fab regions (B) on the FcεRI-bound mutated IgEs assessed by flow cytometry according to some aspect of the disclosure. The cells were incubated with 0.5 μg/mL of the IgE mutants overnight. After washes, the cells were incubated with 10 μg/mL of Fabs or IgGs at 37° C. The remaining IgE amount was assessed as fluorescent antigen binding at indicated time points by flow cytometry.

FIG. 13 illustrates dose response of a standard in a degranulation suppression assay according to some aspect of the disclosure.

FIG. 14 illustrates dose response of a Fab (BH3), a control and a standard in a degranulation suppression assay according to some aspect of the disclosure. The Fab exhibits dose-dependent suppression of degranulation.

FIG. 15 illustrates dose response of omalizumab (Xolair) and a standard in a degranulation suppression assay according to some aspect of the disclosure.

FIG. 16 illustrates binding of rabbit Fabs of BC48 and humanized Fabs of BC48 to Cε2-4 by ELISA according to some aspect of the disclosure.

FIG. 17 illustrates binding of rabbit Fabs of BH3 and humanized Fabs of BH3 to Cε2-4 by ELISA according to some aspect of the disclosure.

DETAILED DESCRIPTION OF THE INVENTION

IgEs are produced by B cells and plasma cells, either centrally or peripherally at the site of inflammation, and are distributed throughout the human body through circulation at a very low concentration. Once picked up by mast cells, the IgE stays on FcεRI for weeks. Therefore, targeting the unbound free IgE cannot remove already bound IgEs on FcεRI for a long time. However, because of the low production, it is not difficult to neutralize unbound IgEs using antibodies such as omalizumab.

Omalizumab (Xolair®) has been developed to neutralize the free IgEs in sera and to block their binding to FcεRI and low-affinity IgE receptors, CD23. Omalizumab is a recombinant humanized IgG1κ monoclonal antibody that mainly binds Cε3 domain of human IgE. The efficacy of omalizumab has been reported for many allergic diseases including allergic asthma 1-5, chronic urticaria 6, 7, nasal polyposis 8, 9, and pollinosis 10, and approved for the treatment of moderate to severe persistent allergic asthma, chronic idiopathic urticaria (CIU) and nasal polyps in the USA. It is also approved for severe pollinosis in Japan. In addition, its benefit in an adjunctive use with immunotherapy has been reported 11. One of the major drawbacks of omalizumab is its slow action. Since omalizumab does not affect the FcεRI-bound IgEs, the reduction of IgE on mast cells takes longer (˜70 days) than that on basophils (˜7 days), depending on their half-lives 12, 13. Therefore, the improvement of allergic disease requires more than two weeks after initiation of the therapy 13.

To improve efficacy, several kinds of IgE-associating molecules have been developed, including ligelizumab 14-18, aεFab 19, MEDI4212 20, 21, DARPins (designed ankyrin repeat proteins) 22-25, Single-domain antibody (sdab) 026 26, quilizumab 27-29, AIMab7195 (former XmAb7195) 30, bispecific IgE/CD3 antibody (bsc-IgE/CD3) 31, and DNA aptamers 321, 33, 34. Most of the substances directly targeting IgE Cε3 to block its binding to IgE receptors, as IgE binds FcεRI and CD23 using Cε3 portion. However, the mode of action varies among the substances; the steric hindrance, allosteric hindrance, and facilitated dissociation mechanisms have been proposed for the blocking and removal activities 35. For example, the binding of omalizumab blocks IgE's binding to CD23 by steric hindrance, caused by a direct overlap of the footprints of omalizumab and human CD23 36, 37. The way omalizumab blocks IgE's binding to FcεRI is different; the binding of omalizumab alters IgE's 3D-conformation to the one that cannot bind FcεRI. This mode is called allosteric hindrance 37. The best example of the facilitated dissociation is DARPin E2_79. DARPin E2_79 shares a small portion of the footprint with FcεRI on IgE molecule, and this competition at that small part is considered to accelerate the dissociation of FcεRI 23. Therefore, the IgE blocking substances may have different blocking and/or removal activities depending on the binding sites.

In addition to Cε3, the Cε2 portion of human IgE has a role in stabilizing the IgE's binding to FcεRI 38. A modified version of omalizumab Fab called FabXol3 has contact with some of Cε2 amino acids 37. An Fab portion of an antibody against mouse Cε2 (clone 6HD5) reduces mast cell activation in vivo and in vitro 39. However, the binding epitope for Fab-6HD5 inside Cε2 has not been elucidated. Furthermore, the homology of the amino acid sequences between human and mouse IgE Cε2-Cε4 is quite low (55% for Cε2-Cε4, and 63% for Cε2), and human IgE does not bind murine FcεRI. Therefore, this cannot be directly extrapolated into human IgE, and it has not been well understood whether antibodies targeting human Cε2 can block and/or remove IgE's binding to its receptors.

In this invention, we have devised several Fab clones that bind mainly to Cε2 of human IgE. The Fab clones were able to not only block IgE's binding to FcεRI and CD23, but also remove already bound IgEs from their receptors. These Fabs had common binding epitopes inside the Cε2 portion that were not described before. Our invention adds another strategy to target IgE, in a faster way than the omalizumab does.

IgEs play a pivotal role in the immediate allergic reaction. In addition, successful applications of an anti-human IgE antibody, omalizumab, to human diseases have proved essential roles of IgEs in various allergic disorders including asthma, chronic idiopathic urticaria, nasal polyps, hay fever, and food allergy.

The Cε2 region of human IgE has been implicated in the stability of IgE on FcεRI. However, it was not clear whether an Fab or IgG targeting Cε2 can inhibit the binding of human IgE to FcεRI and CD23.

In this invention, we first prepared Fab libraries against human IgE that were produced from a rabbit immunized with a recombinant human IgE Cε2-4 fragment and selected by phage display. The Fab fragments of selected clones against Cε2 region were purified and subjected to competition, removal, and degranulation inhibition assays. The binding sites of the selected three Fabs were investigated using a partial chimera fragment of human and mouse Cε2, and further narrowed down using chimera IgEs. The competition and removal activities against human CD23 on cell surface were also assessed.

As a result, 24 clones against Cε2 were isolated from a rabbit Fab library. All these Fab clones competitively inhibited the binding of human IgE to FcεRI. The removal activities were highly correlated with the competitive inhibition activities. Of these, three highly active clones were selected. These did not bind mouse IgEs. Using a recombinant human Cε2 of which the amino acid sequence was partially substituted with that of mouse Cε2, β5-helix region was found to be the common binding region of these Fabs. Further investigation revealed that especially the latter half of the β5-helix region was the essential portion for the inhibitory binding. These Fabs competitively inhibited the binding of human IgEs to human CD23, and removed IgEs bound to CD23. Using mouse bone marrow-derived mast cells expressing human FcεRIα, the removal of IgEs from the mast cell surface was shown to reduce mast cell activation. In summary, Fab clones against human IgE Cε2 region were obtained that elicit inhibition activities on binding of human IgE to its receptors.

Antibody Production

In some embodiments, anti-IgE antibodies are raised by standard protocol by injecting a production animal with an antigenic composition. See, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. When utilizing an entire protein, or a larger section of the protein, antibodies may be raised by immunizing the production animal with the protein and a suitable adjuvant (e.g., Freund's, Freund's complete, oil-in-water emulsions, etc.). When a smaller peptide is utilized, it is advantageous to conjugate the peptide with a larger molecule to make an immunostimulatory conjugate. Commonly utilized conjugate proteins that are commercially available for such use include bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH). In order to raise antibodies to particular epitopes, peptides derived from the full sequence may be utilized. Alternatively, in order to generate antibodies to relatively short peptide portions of the protein target, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as ovalbumin, BSA or KLH.

Polyclonal or monoclonal anti-IgE antibodies can be produced from animals which have been genetically altered to produce human immunoglobulins. A transgenic animal can be produced by initially producing a “knock-out” animal which does not produce the animal's natural antibodies, and stably transforming the animal with a human antibody locus (e.g., by the use of a human artificial chromosome). In such cases, only human antibodies are then made by the animal. Techniques for generating such animals, and deriving antibodies therefrom, are described in U.S. Pat. Nos. 6,162,963 and 6,150,584, incorporated fully herein by reference. Such antibodies can be referred to as human xenogenic antibodies.

Alternatively, anti-IgE antibodies can be produced from phage libraries containing human variable regions. See U.S. Pat. No. 6,174,708, incorporated fully herein by reference.

In some aspects of any of the embodiments disclosed herein, an anti-IGE antibody is produced by a hybridoma.

For monoclonal anti-IgE antibodies, hybridomas may be formed by isolating the stimulated immune cells, such as those from the spleen of the inoculated animal. These cells can then be fused to immortalized cells, such as myeloma cells or transformed cells, which are capable of replicating indefinitely in cell culture, thereby producing an immortal, immunoglobulin-secreting cell line. The immortal cell line utilized can be selected to be deficient in enzymes necessary for the utilization of certain nutrients. Many such cell lines (such as myelomas) are known to those skilled in the art, and include, for example: thymidine kinase (TK) or hypoxanthine-guanine phosphoriboxyl transferase (HGPRT). These deficiencies allow selection for fused cells according to their ability to grow on, for example, hypoxanthine aminopterinthymidine medium (HAT).

In addition, the anti-IgE antibody may be produced by genetic engineering.

Anti-IgE antibodies disclosed herein can have a reduced propensity to induce an undesired immune response in humans, for example, anaphylactic shock, and can also exhibit a reduced propensity for priming an immune response which would prevent repeated dosage with an antibody therapeutic or imaging agent (e.g., the human-anti-murine-antibody “HAMA” response). Such anti-IgE antibodies include, but are not limited to, humanized, chimeric, or xenogenic human anti-IgE antibodies.

Chimeric anti-IgE antibodies can be made, for example, by recombinant means by combining the murine variable light and heavy chain regions (VK and VH), obtained from a murine (or other animal-derived) hybridoma clone, with the human constant light and heavy chain regions, in order to produce an antibody with predominantly human domains. The production of such chimeric antibodies is well known in the art, and may be achieved by standard means (as described, e.g., in U.S. Pat. No. 5,624,659, incorporated fully herein by reference).

The term “humanized” as applies to a non-human (e.g. rodent or primate) antibodies are hybrid immunoglobulins, immunoglobulin chains or fragments thereof which contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, rabbit or primate having the desired specificity, affinity and capacity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, the humanized antibody may comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. These modifications are made to further refine and optimize antibody performance and minimize immunogenicity when introduced into a human body. In some examples, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence. The humanized antibody may also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.

Humanized antibodies can be engineered to contain human-like immunoglobulin domains, and incorporate only the complementarity-determining regions of the animal-derived antibody. This can be accomplished by carefully examining the sequence of the hyper-variable loops of the variable regions of a monoclonal antigen binding unit or monoclonal antibody, and fitting them to the structure of a human antigen binding unit or human antibody chains. See, e.g., U.S. Pat. No. 6,187,287, incorporated fully herein by reference.

Methods for humanizing non-human antibodies are well known in the art. “Humanized” antibodies are antibodies in which at least part of the sequence has been altered from its initial form to render it more like human immunoglobulins. In some versions, the heavy (H) chain and light (L) chain constant (C) regions are replaced with human sequence. This can be a fusion polypeptide comprising a variable (V) region and a heterologous immunoglobulin C region. In some versions, the complementarity determining regions (CDRs) comprise non-human antibody sequences, while the V framework regions have also been converted to human sequences. See, for example, EP 0329400. In some versions, V regions are humanized by designing consensus sequences of human and mouse V regions, and converting residues outside the CDRs that are different between the consensus sequences.

In principle, a framework sequence from a humanized antibody can serve as the template for CDR grafting; however, it has been demonstrated that straight CDR replacement into such a framework can lead to significant loss of binding affinity to the antigen. Glaser et al. (1992) J. Immunol. 149:2606; Tempest et al. (1992) Biotechnology 9:266; and Shalaby et al. (1992) J. Exp. Med. 17:217. The more homologous a human antibody (HuAb) is to the original murine antibody (muAb), the less likely that the human framework will introduce distortions into the murine CDRs that could reduce affinity. Based on a sequence homology search against an antibody sequence database, the HuAb IC4 provides good framework homology to muM4TS.22, although other highly homologous HuAbs would be suitable as well, especially kappa L chains from human subgroup I or H chains from human subgroup III. Kabat et al. (1987). Various computer programs such as ENCAD (Levitt et al. (1983) J. Mol. Biol. 168:595) are available to predict the ideal sequence for the V region. The invention thus encompasses HuAbs with different variable (V) regions. It is within the skill of one in the art to determine suitable V region sequences and to optimize these sequences. Methods for obtaining antibodies with reduced immunogenicity are also described in U.S. Pat. No. 5,270,202 and EP 699,755.

Humanized antibodies can be prepared by a process of analysis of the parental sequences and various conceptual humanized products using three dimensional models of the parental and humanized sequences. Three dimensional immunoglobulin models are familiar to those skilled in the art. Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen. In this way, FR residues can be selected and combined from the consensus and import sequence so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved.

A process for humanization of subject antigen binding units can be as follows. The best-fit germline acceptor heavy and light chain variable regions are selected based on homology, canonical structure and physical properties of the human antibody germlines for grafting. Computer modeling of mVH/VL versus grafted hVH/VL is performed and prototype humanized antibody sequence is generated. If modeling indicated a need for framework back-mutations, second variant with indicated FW changes is generated. DNA fragments encoding the selected germline frameworks and murine CDRs are synthesized. The synthesized DNA fragments are subcloned into IgG expression vectors and sequences are confirmed by DNA sequencing. The humanized antibodies are expressed in cells, such as 293F and the proteins are tested, for example in MDM phagocytosis assays and antigen binding assays. The humanized antigen binding units are compared with parental antigen binding units in antigen binding affinity, for example, by FACS on cells expressing the target antigen. If the affinity is greater than 2-fold lower than parental antigen binding unit, a second round of humanized variants can be generated and tested as described above.

As noted above, an anti-IgE antibody can be either “monovalent” or “multivalent.” Whereas the former has one binding site per antigen-binding unit, the latter contains multiple binding sites capable of binding to more than one antigen of the same or different kind. Depending on the number of binding sites, antigen binding units may be bivalent (having two antigen-binding sites), trivalent (having three antigen-binding sites), tetravalent (having four antigen-binding sites), and so on.

Multivalent anti-IgE antibodies can be further classified on the basis of their binding specificities. A “monospecific” anti-IgE antibody is a molecule capable of binding to one or more antigens of the same kind. A “multispecific” anti-IgE antibody is a molecule having binding specificities for at least two different antigens. While such molecules normally will only bind two distinct antigens (i.e. bispecific anti-IgE antibodies), antibodies with additional specificities such as trispecific antibodies are encompassed by this expression when used herein. This disclosure further provides multispecific anti-IgE antibodies. Multispecific anti-IgE antibodies are multivalent molecules capable of binding to at least two distinct antigens, e.g., bispecific and trispecific molecules exhibiting binding specificities to two and three distinct antigens, respectively.

Polynucleotides and Vectors

In some embodiments, the present disclosure provides isolated nucleic acids encoding any of the anti-IgE antibodies disclosed herein. In another embodiment, the present disclosure provides vectors comprising a nucleic acid sequence encoding any anti-IgE antibody disclosed herein. In some embodiments, this invention provides isolated nucleic acids that encode a light-chain CDR and a heavy-chain CDR of an anti-IgE antibody disclosed herein.

The subject anti-IgE antibodies can be prepared by recombinant DNA technology, synthetic chemistry techniques, or a combination thereof. For instance, sequences encoding the desired components of the anti-IgE antibodies, including light chain CDRs and heavy chain CDRs are typically assembled cloned into an expression vector using standard molecular techniques know in the art. These sequences may be assembled from other vectors encoding the desired protein sequence, from PCR-generated fragments using respective template nucleic acids, or by assembly of synthetic oligonucleotides encoding the desired sequences. Expression systems can be created by transfecting a suitable cell with an expressing vector which comprises an anti-IgE antibody of interest.

Nucleotide sequences corresponding to various regions of light or heavy chains of an existing antibody can be readily obtained and sequenced using convention techniques including but not limited to hybridization, PCR, and DNA sequencing. Hybridoma cells that produce monoclonal antibodies serve as a preferred source of antibody nucleotide sequences. A vast number of hybridoma cells producing an array of monoclonal antibodies may be obtained from public or private repositories. The largest depository agent is American Type Culture Collection (atcc.org), which offers a diverse collection of well-characterized hybridoma cell lines.

Alternatively, antibody nucleotides can be obtained from immunized or non-immunized rodents or humans, and form organs such as spleen and peripheral blood lymphocytes. Specific techniques applicable for extracting and synthesizing antibody nucleotides are described in Orlandi et al. (1989) Proc. Natl. Acad. Sci. U.S.A 86: 3833-3837; Larrick et al. (1989) Biochem. Biophys. Res. Commun. 160:1250-1255; Sastry et al. (1989) Proc. Natl. Acad. Sci., U.S.A. 86: 5728-5732; and U.S. Pat. No. 5,969,108.

Polynucleotides encoding anti-IgE antibodies can also be modified, for example, by substituting the coding sequence for human heavy and light chain constant regions in place of the homologous non-human sequences. In that manner, chimeric antibodies are prepared that retain the binding specificity of the original anti-IgE antibody.

Host Cells

In some embodiments, the present disclosure provides host cells expressing any one of the anti-IgE antibodies disclosed herein. A subject host cell typically comprises a nucleic acid encoding any one of the anti-IgE antibodies disclosed herein.

The invention provides host cells transfected with the polynucleotides, vectors, or a library of the vectors described above. The vectors can be introduced into a suitable prokaryotic or eukaryotic cell by any of a number of appropriate means, including electroporation, microprojectile bombardment; lipofection, infection (where the vector is coupled to an infectious agent), transfection employing calcium chloride, rubidium chloride, calcium phosphate, DEAE-dextran, or other substances. The choice of the means for introducing vectors will often depend on features of the host cell.

For most animal cells, any of the above-mentioned methods is suitable for vector delivery. Preferred animal cells are vertebrate cells, preferably mammalian cells, capable of expressing exogenously introduced gene products in large quantity, e.g. at the milligram level. Non-limiting examples of preferred cells are NIH3T3 cells, COS, HeLa, and CHO cells.

Once introduced into a suitable host cell, expression of the anti-IgE antibodies can be determined using any nucleic acid or protein assay known in the art. For example, the presence of transcribed mRNA of light chain CDRs or heavy chain CDRs, or the anti-IGE antibody can be detected and/or quantified by conventional hybridization assays (e.g. Northern blot analysis), amplification procedures (e.g. RT-PCR), SAGE (U.S. Pat. No. 5,695,937), and array-based technologies (see e.g. U.S. Pat. Nos. 5,405,783, 5,412,087 and 5,445,934), using probes complementary to any region of a polynucleotide that encodes the anti-IGE antibody.

Expression of the vector can also be determined by examining the expressed anti-IgE antibody. A variety of techniques are available in the art for protein analysis. They include but are not limited to radioimmunoassays, ELISA (enzyme linked immunoradiometric assays), “sandwich” immunoassays, immunoradiometric assays, in situ immunoassays (using e.g., colloidal gold, enzyme or radioisotope labels), western blot analysis, immunoprecipitation assays, immunofluorescent assays, and SDS-PAGE.

NON-LIMITING EMBODIMENTS

The present disclosure is also described and demonstrated by way of the following non-limiting embodiments. However, the use of these and other examples anywhere in the specification is illustrative only and in no way limits the scope and meaning of the disclosure or of any exemplified term. Likewise, the disclosure is not limited to any particular preferred embodiment or aspect described herein. Indeed, suitable modifications and variations may be apparent to those skilled in the art upon reading this specification, and such variations can be made without departing from the invention in spirit or in scope.

• • 1. An antigen binding polypeptide, wherein the polypeptide exhibits specific binding to an IgE.
  • 2. The antigen binding polypeptide of embodiment 1, wherein the binding of the antigen binding polypeptide to the IgE disrupts interaction between the IgE and at least one Fcε receptor.
  • 3. The antigen binding polypeptide of embodiment 2, wherein the disrupted interaction comprises blocking an unbound IgE from binding to the at least one Fcε receptor.
  • 4. The antigen binding polypeptide of embodiment 2-3, wherein the disrupted interaction comprises dissociating a bound IgE from the at least one Fcε receptor.
  • 5. The antigen binding polypeptide of embodiment 2-4, wherein the disrupted interaction results in suppression of degranulation.
  • 6. The antigen binding polypeptide of embodiment 2-5, wherein the at least one Fcε receptor comprises FcεRI.
  • 7. The antigen binding polypeptide of embodiment 2-5, wherein the at least one Fcε receptor comprises CD23.
  • 8. The antigen binding polypeptide of embodiment 2-5, wherein the at least one Fcε receptor comprises FcεRI and CD23.
  • 9. The antigen binding polypeptide of embodiment 1-8, wherein the antigen binding polypeptide specifically binds to at least one amino acid residue in β5-helix region of the Cε2, wherein the β5-helix region is the combination of helix, β5-helix joint, and lower half of β5 that connects to helix of Cε2.
  • 10. The antigen binding polypeptide of embodiment 9, wherein the antigen binding polypeptide specifically binds to at least one amino acid residue in the helix of Cε2.
  • 11. The antigen binding polypeptide of embodiment 9-10, wherein the antigen binding polypeptide specifically binds to at least one amino acid residue in the β5-helix joint of Cε2.
  • 12. The antigen binding polypeptide of embodiment 9-11, wherein the antigen binding polypeptide specifically binds to at least one amino acid residue in the lower half of β5 that connects to helix of Cε2.
  • 13. The antigen binding polypeptide of embodiment 9-12, wherein the antigen binding polypeptide does not bind to amino acid residue T298 of Cε2.
  • 14. The antigen binding polypeptide of embodiment 9-13, wherein the antigen binding polypeptide binds to at least two amino acid residues in the β5-Cε2 helix region.
  • 15. The antigen binding polypeptide of embodiment 1-14, wherein the antigen binding polypeptide does not bind to β3 region of Cε2.
  • 16. The antigen binding polypeptide of embodiment 1-14, wherein the antigen binding polypeptide does not bind to β4 region of Cε2.
  • 17. The antigen binding polypeptide of embodiment 1-14, wherein the antigen binding polypeptide does not bind to β3 or β4 region of Cε2.
  • 18. The antigen binding polypeptide of embodiment 1-17, comprising at least one amino acid sequence selected from SEQ ID Nos 1-25.
  • 19. The antigen binding polypeptide of embodiment 1-18, comprising at least one amino acid sequence selected from SEQ ID Nos 26-50.
  • 20. The antigen binding polypeptide of embodiment 1-19, comprising at least one amino acid sequence selected from SEQ ID Nos 51-150, DAS, DVS, LSS, KAS, GAS, RAS, TTS, EAS, KTS, and SEQ ID Nos 176-200.
  • 21. An antibody or a fragment thereof, comprising a Fab region that specifically binds to an IgE.
  • 22. The antibody or fragment of embodiment 21, wherein the binding of the Fab to the IgE disrupts interaction between the IgE and at least one Fcε receptor.
  • 23. The antibody or fragment of embodiment 22, wherein the disrupted interaction comprises blocking an unbound IgE from binding to the at least one Fcε receptor.
  • 24. The antibody or fragment of embodiment 22-23, wherein the disrupted interaction comprises dissociating a bound IgE from the at least one Fcε receptor.
  • 25. The antibody or fragment of embodiment 22-24, wherein the disrupted interaction results in suppression of degranulation.
  • 26. The antibody or fragment of embodiment 22-25, wherein the at least one Fcε receptor comprises FcεRI.
  • 27. The antigen binding polypeptide of embodiment 22-25, wherein the at least one Fcε receptor comprises CD23.
  • 28. The antibody or fragment of embodiment 22-25, wherein the at least one Fcε receptor comprises FcεRI and CD23.
  • 29. The antibody or fragment of embodiment 21-28, wherein the Fab region specifically binds to at least one amino acid residue in β5-helix region of the Cε2, wherein the β5-helix region is the combination of helix, β5-helix joint, and lower half of β5 that connects to helix of Cε2.
  • 30. The antibody or fragment of embodiment 29, wherein the Fab region specifically binds to at least one amino acid residue in the helix of Cε2.
  • 31. The antibody or fragment of embodiment 29-30, wherein the Fab region specifically binds to at least one amino acid residue in the β5-helix joint of Cε2.
  • 32. The antibody or fragment of embodiment 29-31, wherein the Fab region specifically binds to at least one amino acid residue in the lower half of β5 that connects to helix of Cε2.
  • 33. The antibody or fragment of embodiment 29-32, wherein the Fab region does not bind to amino acid residue T298 of Cε2.
  • 34. The antibody or fragment of embodiment 29-33, wherein the Fab region binds to at least two amino acid residues in the β5-Cε2 helix region.
  • 35. The antibody or fragment of embodiment 21-34, wherein the Fab region does not bind to 33 region of Cε2.
  • 36. The antibody or fragment of embodiment 21-34, wherein the Fab region does not bind to β4 region of Cε2.
  • 37. The antibody or fragment of embodiment 21-34, wherein the Fab region does not bind to β or β4 region of Cε2.
  • 38. The antibody or fragment of embodiment 21-37, wherein the antibody is a bispecific antibody or a binding fragment thereof.
  • 39. The antibody or fragment of embodiment 21-38, wherein the antibody comprises a monovalent Fab′, a divalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or binding fragment thereof.
  • 40. The antibody or fragment of embodiment 21-39, wherein the Fab region comprises at least one heavy chain sequence selected from SEQ ID Nos 1-25.
  • 41. The antibody or fragment of embodiment 21-40, wherein the Fab region comprises at least one light chain sequence selected from SEQ ID Nos 26-50.
  • 42. The antibody or fragment of embodiment 21-41, wherein the Fab region comprises at least one complementarity determining region (CDR) selected from SEQ ID Nos 51-150, DAS, DVS, LSS, KAS, GAS, RAS, TTS, EAS, KTS, and SEQ ID Nos 176-200.
  • 43. The antibody or fragment of embodiment 21-42, wherein the antibody exhibits a K_D of less than 1 nM, 1.2 nM, 2 nM, 5 nM, 10 nM, 13.5 nM, 15 nM, 20 nM, 25 nM, or 30 nM.
  • 44. The antibody or fragment of embodiment 21-43, wherein the antibody comprises a humanized antibody.
  • 45. An antibody or a fragment thereof, having Fab region comprising at least one heavy chain sequence selected from SEQ ID Nos 1-25.
  • 46. An antibody or a fragment thereof, having Fab region comprising at least one light chain sequence selected from SEQ ID Nos 26-50.
  • 47. An antibody or a fragment thereof, having Fab region comprising at least one heavy chain sequence selected from SEQ ID Nos 1-25 and at least one light chain sequence selected from SEQ ID Nos 26-50.
  • 48. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 1 and a light chain sequence of SEQ ID No 26.
  • 49. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 2 and a light chain sequence of SEQ ID No 27.
  • 50. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 3 and a light chain sequence of SEQ ID No 28.
  • 51. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 4 and a light chain sequence of SEQ ID No 29.
  • 52. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 5 and a light chain sequence of SEQ ID No 30.
  • 53. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 6 and a light chain sequence of SEQ ID No 31.
  • 54. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 7 and a light chain sequence of SEQ ID No 32.
  • 55. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 8 and a light chain sequence of SEQ ID No 33.
  • 56. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 9 and a light chain sequence of SEQ ID No 34.
  • 57. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 10 and a light chain sequence of SEQ ID No 35.
  • 58. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 11 and a light chain sequence of SEQ ID No 36.
  • 59. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 12 and a light chain sequence of SEQ ID No 37.
  • 60. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 13 and a light chain sequence of SEQ ID No 38.
  • 61. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 14 and a light chain sequence of SEQ ID No 39.
  • 62. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 15 and a light chain sequence of SEQ ID No 40.
  • 63. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 16 and a light chain sequence of SEQ ID No 41.
  • 64. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 17 and a light chain sequence of SEQ ID No 42.
  • 65. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 18 and a light chain sequence of SEQ ID No 43.
  • 66. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 19 and a light chain sequence of SEQ ID No 44.
  • 67. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 20 and a light chain sequence of SEQ ID No 45.
  • 68. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 21 and a light chain sequence of SEQ ID No 46.
  • 69. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 22 and a light chain sequence of SEQ ID No 47.
  • 70. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 23 and a light chain sequence of SEQ ID No 48.
  • 71. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 24 and a light chain sequence of SEQ ID No 49.
  • 72. An antibody or a fragment thereof, having Fab region comprising a heavy chain sequence of SEQ ID No 25 and a light chain sequence of SEQ ID No 50.
  • 73. An antibody or a fragment thereof, having Fab region comprising an HCDR1 selected from SEQ ID Nos 51-75.
  • 74. The antibody or fragment of embodiment 73, having Fab region comprising an HCDR2 selected from SEQ ID Nos 76-100.
  • 75. The antibody or fragment of embodiment 73-74, having Fab region comprising an HCDR3 selected from SEQ ID Nos 101-125.
  • 76. The antibody or fragment of embodiment 73-75, having Fab region comprising an LCDR1 selected from SEQ ID Nos 126-150.
  • 77. The antibody or fragment of embodiment 73-76, having Fab region comprising an LCDR2 selected from DAS, DVS, LSS, KAS, GAS, RAS, TTS, EAS, and KTS.
  • 78. The antibody or fragment of embodiment 73-77, having Fab region comprising an LCDR3 selected from SEQ ID Nos 176-200.
  • 79. The antibody or fragment of embodiment 45-78, wherein the antibody exhibits a K_D of less than 1 nM, 1.2 nM, 2 nM, 5 nM, 10 nM, 13.5 nM, 15 nM, 20 nM, 25 nM, or 30 nM.
  • 80. The antibody or fragment of embodiment 45-79, wherein the antibody comprises a humanized antibody.
  • 81. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201-202.
  • 82. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a light chain variable region selected from SEQ ID Nos 203-206.
  • 83. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201-202, and a light chain variable region selected from SEQ ID Nos 203-206.
  • 84. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201, and a light chain variable region selected from SEQ ID Nos 203-204.
  • 85. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 202, and a light chain variable region selected from SEQ ID Nos 205-206.
  • 86. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207-208.
  • 87. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a light chain full sequence selected from SEQ ID Nos 209-212.
  • 88. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207-208, and a light chain variable region selected from SEQ ID Nos 209-212.
  • 89. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207, and a light chain variable region selected from SEQ ID Nos 209-210.
  • 90. A humanized antibody or a fragment thereof, wherein the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 208, and a light chain variable region selected from SEQ ID Nos 211-212.
  • 91. A complex comprising the antigen binding polypeptide of embodiment 1-20 or the antibody or fragment of embodiment 21-90, wherein the complex comprises the polypeptide or antibody bound to IgE protein.
  • 92. A method of disrupting an interaction between IgE and at least one Fcε receptor, comprising:
    • contacting a cell expressing the at least one Fcε receptor with an antigen binding polypeptide that specifically binds to β5-helix region of the Cε2, wherein the β5-helix region is the combination of helix, β5-helix joint, and lower half of β5 that connects to helix of Cε2.
  • 93. The method of embodiment 92, wherein the antigen binding polypeptide specifically binds to at least one amino acid residue in the helix of Cε2.
  • 94. The method of embodiment 92-93, wherein the antigen binding polypeptide specifically binds to at least one amino acid residue in the β5-helix joint of Cε2.
  • 95. The method of embodiment 92-94, wherein the antigen binding polypeptide specifically binds to at least one amino acid residue in the lower half of β5 that connects to helix of Cε2.
  • 96. The method of embodiment 92-95, wherein the disrupted interaction comprises blocking an unbound IgE from binding to the at least one Fcε receptor.
  • 97. The method of embodiment 92-96, wherein the disrupted interaction comprises dissociating a bound IgE from the at least one Fcε receptor.
  • 98. The method of embodiment 96-97, wherein the disrupted interaction results in suppression of degranulation.
  • 99. The method of embodiment 92-98, wherein the at least one Fcε receptor comprises FcεRI.
  • 100. The method of embodiment 92-98, wherein the at least one Fcε receptor comprises CD23.
  • 101. The method of embodiment 92-98, wherein the at least one Fcε receptor comprises FcεRI and CD23.
  • 102. The method of embodiment 92-101, wherein the Fab region does not bind to amino acid residue T298 of Cε2.
  • 103. The method of embodiment 92-102, wherein the Fab region binds to at least two amino acid residues in the β5-Cε2 helix region.
  • 104. The method of embodiment 92-103, wherein the antigen binding polypeptide does not bind to β3 region of Cε2.
  • 105. The method of embodiment 92-103, wherein the antigen binding polypeptide does not bind to β4 region of Cε2.
  • 106. The method of embodiment 92-103, wherein the antigen binding polypeptide does not bind to β3 or β4 region of Cε2.
  • 107. The method of embodiment 92-106, wherein the antigen binding polypeptide is an antibody or a binding fragment thereof.
  • 108. The method of embodiment 107, wherein the antibody comprises a monovalent Fab′, a divalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or binding fragment thereof.
  • 109. The method of embodiment 107-108, wherein the Fab region comprises at least one heavy chain sequence selected from SEQ ID Nos 1-25.
  • 110. The method of embodiment 107-109, wherein the Fab region comprises at least one light chain sequence selected from SEQ ID Nos 26-50.
  • 111. The method of embodiment 107-110, wherein the Fab region comprises at least one complementarity determining region (CDR) selected from SEQ ID Nos 51-150, DAS, DVS, LSS, KAS, GAS, RAS, TTS, EAS, KTS, and SEQ ID Nos 176-200.
  • 112. The method of embodiment 107-111, wherein the antibody exhibits a K_D of less than 1 nM, 1.2 nM, 2 nM, 5 nM, 10 nM, 13.5 nM, 15 nM, 20 nM, 25 nM, or 30 nM.
  • 113. The method of embodiment 107-112, wherein the antibody comprises a humanized antibody.
  • 114. The method of embodiment 92-113, wherein the interaction between IgE and at least one Fcε receptor is associated with an allergic condition.
  • 115. The method of embodiment 114, wherein the allergic condition is selected from asthma, chronic idiopathic urticaria, nasal polyps, hay fever, or food allergy.

NON-LIMITING EXAMPLES

The present disclosure is also described and demonstrated by way of the following non-limiting examples. However, the use of these and other examples anywhere in the specification is illustrative only and in no way limits the scope and meaning of the disclosure or of any exemplified term. Likewise, the disclosure is not limited to any particular preferred example or aspect described herein. Indeed, suitable modifications and variations may be apparent to those skilled in the art upon reading this specification, and such variations can be made without departing from the invention in spirit or in scope.

Example 1—The Development of Anti-IgE Antibodies from an Immunized Rabbit

New Zealand White rabbits were immunized with a recombinant IgE Cε2-4 protein. Phage display libraries were constructed from the bone marrow and spleen and selected against a recombinant IgE Cε2-4 protein. The clones that showed specific binding to IgE Cε2-4 protein by ELISA were sequenced and their complementarity determining regions (CDRs) were analyzed (FIGS. 1-4). These clones were expressed as Fab with 6×His tag in HEK293 cells and purified using Ni-NTA column chromatography.

Example 2—Three Fabs Inhibit Binding of Human IgE to Human FcεRI

We investigated whether the newly invented Fabs can inhibit the binding of human IgE to human FcεRI. Human FcεRI is a heterotetrameric protein, which is composed of one α-chain, one β-chain, and two γ-chains. Using a BaF/3 cell line retrovirally transduced with these α, β, and γ-chains of human FcεRI, we evaluated the binding of human IgEs preincubated with three Fabs: 21626B-C4-8 (BC48)(SEQ ID No. 24, 49, 74, 99, 124, 149, KTS, and SEQ ID No. 199), 21626B-H3 (BH3)(SEQ ID No. 20, 45, 70, 95, 120, 145, RAS, and SEQ ID No.195), and 21626B-A8 (BA8)(SEQ ID No. 21, 46, 71, 96, 121EAS, 171, and SEQ ID No. 196) or Xolair to the cell surface human FcεRI. To avoid the potential interference of the Fabs with the bound IgE detection, we used fluorescently labeled antigen to measure the IgEs amount. Interestingly, all the three Fabs inhibited the binding of IgE to the cell surface human FcεRI, at a lower molar ratio compared to the commercially available Xolair (FIG. 5).

Example 3—Three Fabs Remove Human IgE and Suppress Antigen-Stimulated Degranulation of Human FcεRIα-Transgenic Murine Bone Marrow-Derived Mast Cells (BMMCs)

We further evaluated whether our Fabs can remove IgEs already bound to human FcεRI on cell surface. The three Fabs, but not the control Fabs that does not target human IgE, could remove IgEs in a dose dependent manner from the cell surface of human FcεRIα-transgenic BMMCs (FIG. 6A). Furthermore, the removal coincided with the reduced antigen-dependent activation of BMMCs (FIG. 6B), indicating that the three Fabs can suppress the mast cell reaction through removal of the bound IgEs

Example 4—Three Fabs Exhibit Inhibition and Removal Activities on IgE's Binding to Low-Affinity Receptor CD2

To invest the effects of the Fabs to IgE's binding to the low-affinity IgE receptor, CD23, we performed competition and removal assays using a BaF/3 cell line retrovirally transduced with human CD23. The amount of IgEs on cell surface was measured by the binding capacity of the fluorescently labeled antigens. We found that the preincubation of human IgE with the three Fabs strongly inhibited the binding to cell surface CD23 (FIG. 7A). Furthermore, the Fabs showed various removal activities within 1 h on the already bound IgE (FIG. 7B)

Example 5—the Three Fabs Bind β5-Helix Region of Cε2 in a Tertiary Structure-Dependent Manner

To find the binding sites of the three Fabs, we prepared recombinant His6-tagged Cε2 protein of human IgE and evaluated binding of the Fabs to the raw, boiled, and PNGaseF-treated boiled Cε2 by ELISA. The bindings of Fabs were abolished by boiling, suggesting that the tertiary structure is important for the binding of Fabs to the Cε2 (FIG. 8A). In addition, the treatment of recombinant Cε2 with PNGaseF did not affect the binding of Fabs to Cε2, suggesting that the PNGaseF-accessible N-glycan chains are not involved in the binding sites (FIG. 8B). To further narrow down the Fab binding sites in Cε2, we tried to substitute parts of the human Cε2 with the corresponding part of murine Cε2. Importantly, the three Fabs did not bind murine IgE (FIG. 8C). Because Cε2 of the two species are composed of 7 β-sheets and one α-helix (FIG. 8D), we expressed 7 chimera Cε2 proteins in HEK293T cells and evaluated the binding of Fabs to them. Interestingly, substitution of β5-helix region of human Cε2 with that of murine β5-helix abolished all three Fabs' binding (FIG. 8E). These results indicate that the three Fabs have critical binding sites at β5-helix region in common.

Example 6—The Detailed Binding Sites in the β5-Helix Region

There were 9 amino acids that were different between human and mouse β5-helix region of Cε2 (FIG. 9). Therefore, we prepared chimera human IgEs, in which the parts of β5-helix region were substituted with those of murine IgEs (FIG. 9A). The binding of the three Fabs were abolished by the mutation of the middle to C-terminal of the β5-helix region (FIG. 9B). In addition, the binding of two Fabs were partially reduced by the mutation in β5 (FIG. 9B). There results indicate that the critical binding sites inside β5-helix region includes at least the α-helix region, although β5-region may also be involved.

Example 7—Mutations of β5-Helix Regions Did not Affect IgE's Functions

Because binding of the three Fabs removed human IgEs from the cell surface FcεRI, and because human IgEs does not bind murine FcεRI, we tested whether the substitution of the human β5-helix region of Cε2 with murine sequences can affect the binding functions of human IgE. All the human chimera IgEs evaluated in FIG. 9 bound to cell-surface FcεRI and captured different doses of fluorescently labeled antigens at the similar levels as wild-type IgEs (FIG. 10A). The antigen binding levels were similar 3 and 6 h after washing out the IgEs, indicating that the stability of IgEs on the cell surface FcεRI is also unaffected by the introduced mutations (FIGS. 10B and C). These results suggest that the β5-helix substitution does not affect IgE's intrinsic binding functions to bind to FcεRI.

Example 8—the Inhibition of IgE's Binding to the FcεRI is Fab-Binding Dependent

Using these IgEs, we tested the Fab's ability to inhibit the binding to the cell surface FcεRI. As expected, the mutations of Fabs' critical binding sites abolished the competitive inhibition of IgE's binding to cell surface FcεRI (FIG. 11). Furthermore, for the β5-mutated IgEs, the competition activities were correlated with the binding affinity (FIGS. 9B and 11). These results indicated that the binding inhibition effects were Fab-binding dependent.

Example 9—the Removal of Pre-Bound IgEs on Cell Surface FcεRI is Fab-Binding Dependent

We further determined whether the Fabs' removal effects are dependent on the Fab binding. Again, the mutations of Fabs' critical binding sites abolished the removal of pre-bound IgEs on cell surface FcεRI (FIG. 12A). The similar, but stronger effects were observed when the IgG versions of the Fab clones were used (FIG. 12B). In both cases, the removal activities for the j5 region were correlated with the binding affinity (FIGS. 9B and 11). These results indicated that the removal effects were Fab-binding dependent.

Example 10—Humanized Anti-IgEs Antibodies (BC48 and BH3)

BC48 and BH3 were humanized by grafting CDRs into human germline genes. Humanized Fabs were expressed in HEK293 cells as a 6×his tag protein and purified using a Ni-NTA column. Recombinant Cε2-4 was coated at 1 μg/mL in PBS at 4° C. overnight. The wells were washed 3 times with PBS and blocked with 1% BSA/PBS. The purified Fabs were serially diluted and incubated with the antigen at RT for 1 hour. The wells were washed and the bound rabbit Fabs were detected with peroxidase conjugated goat anti-rabbit IgG F(ab′)2 (ThermoFisher Scientific 31461) and human Fabs were detected with peroxidase conjugated goat anti-human IgG F(ab′)2 (Jackson Immuno Research 109-035-097). Humanized Fabs showed equivalent binding to Cε2-4, as shown in FIGS. 16 and 17.

Sequence Listings

Heavy Chain Sequences

Listed below are heavy chain sequences of certain non-limiting anti-IgE antibodies, identified by name (e.g. “21626S-D5”) and ID number (e.g. “SEQ ID No. 1”).

21626S-D5 SEQ ID No. 1, 213, 214
1:	ValGlnLeuGlnGlnProGlyAlaGluLeuValLysProGlyAlaSerValLysLeuSer
	GTCCAACTGCAGCAGCCTGGAGCTGAACTGGTGAAACCCGGGGCATCAGTGAAGCTGTCC
	---------!---------!---------!---------!---------!---------!	60
1	CAGGTTGACGTCGTCGGACCTCGACTTGACCACTTTGGGCCCCGTAGTCACTTCGACAGG
1:	CysLysAlaSerGlyAspThrPheThrGluTyrIleIleHisTrpValLysGlnArgSer
	TGCAAGGCTTCTGGCGACACCTTCACTGAGTATATTATACACTGGGTAAAGCAGAGGTCT
61	---------!---------!---------!---------!---------!---------!	120
	ACGTTCCGAAGACCGCTGTGGAAGTGACTCATATAATATGTGACCCATTTCGTCTCCAGA
1:	GlyGlnGlyLeuGluTrpIleGlyTrpLeuSerProGlySerGlyAsnIleLysTyrAsn
	GGACAGGGTCTTGAGTGGATTGGGTGGTTATCCCCTGGAAGTGGTAATATAAAGTATAAT
121	---------!---------!---------!---------!---------!---------!	180
	CCTGTCCCAGAACTCACCTAACCCACCAATAGGGGACCTTCACCATTATATTTCATATTA
1:	GluLysPheLysAspLysAlaThrLeuThrAlaAspLysSerSerSerThrValTyrMet
	GAGAAATTCAAGGACAAGGCCACATTGACTGCGGACAAATCCTCCAGCACAGTCTATATG
181	---------!---------!---------!---------!---------!---------!	240
	CTCTTTAAGTTCCTGTTCCGGTGTAACTGACGCCTGTTTAGGAGGTCGTGTCAGATATAC
1:	GluLeuSerArgLeuThrSerGluAspSerAlaValTyrPheCysAlaArgHisGluVal
	GAGCTTAGTAGATTGACATCTGAAGACTCTGCGGTCTATTTCTGTGCAAGACACGAAGTG
	---------!---------!---------!---------!---------!---------!
241	CTCGAATCATCTAACTGTAGACTTCTGAGACGCCAGATAAAGACACGTTCTGTGCTTCAC	300
1:	GlySerTyrAlaMetAspTyrTrpGlyGlnGlyThrSerValThrValSerSer
	GGGTCTTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA
301	---------!---------!---------!---------!---------!----	354
	CCCAGAATACGATACCTGATGACCCCAGTTCCTTGGAGTCAGTGGCAGAGGAGT
21626B-B9 SEQ ID No. 2, 215, 216
1:	GlnThrValLysGluSerGluGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGACGGTGAAGGAGTCCGAGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTGACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCTGCCACTTCCTCAGGCTCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGACTGG
1:	CysThrValSerGlyPheSerLeuSerAsnTyrAlaMetThrTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAGTAACTATGCAATGACCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTCATTGATACGTTACTGGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTrpIleGlyThrIleSerSerGlyGlySerThrTyrTyrAlaSer
	GGGAAGGGGCTGGAATGGATCGGAACCATTAGTAGTGGTGGTAGTACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTACCTAGCCTTGGTAATCATCACCACCATCATGTATGATGCGCTCG
1:	GlyAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuLysIleThr
	GGGGCGAAAGGCCGATTCACCATCTCCAAGACCTCGACCACGGTGGATCTGAAGATCACC
181	---------!---------!---------!---------!---------!---------!	240
	CCCCGCTTTCCGGCTAAGTGGTAGAGGTTCTGGAGCTGGTGCCACCTAGACTTCTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyValGlyGlyGlyAsn
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTGTTGGTGGTGGTAAT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCACAACCACCACCATTA
1:	TyrTyrGluHisPheAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	TATTATGAGCACTTTAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!----	354
	ATAATACTCGTGAAATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-H8 SEQ ID No. 3, 217, 218
1:	GlnSerValGluGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCCACCTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrAlaSerGlyPheSerLeuSerThrTyrSerMetSerTrpValArgGlnAlaPro
	TGCACAGCCTCTGGATTCTCCCTCAGTACCTACTCCATGAGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCGGAGACCTAAGAGGGAGTCATGGATGAGGTACTCGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTrpIleGlyIleIleSerSerSerGlyAsnThrTyrTyrAlaSer
	GGGAAGGGGCTGGAATGGATCGGAATCATTAGTAGTAGTGGTAACACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTACCTAGCCTTAGTAATCATCATCACCATTGTGTATGATGCGCTCG
1:	TrpAlaLysGlyArgPheThrIleSerLysSerSerThrThrValAspLeuLysIleThr
	TGGGCGAAAGGCCGATTCACCATCTCCAAGTCCTCGACCACGGTGGATCTGAAAATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTCCGGCTAAGTGGTAGAGGTTCAGGAGCTGGTGCCACCTAGACTTTTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyValGlyTyrAsnAsn
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTGTTGGTTATAATAAT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCACAACCAATATTATTA
1:	TyrTyrGluHisPheAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	TATTATGAGCACTTTAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!----	354
	ATAATACTCGTGAAATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626S-E6 SEQ ID No. 4, 219, 220
1:	GlnSerValLysGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGTCGGTGAAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCCACTTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrValSerGlyPheSerLeuSerAsnTyrAlaMetSerTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAGTAACTATGCAATGAGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTCATTGATACGTTACTCGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTrpIleGlyIleIleSerSerGlyAlaSerThrTyrTyrAlaSer
	GGGAAGGGGCTGGAATGGATCGGAATCATTAGTAGTGGTGCTAGCACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTACCTAGCCTTAGTAATCATCACCACGATCGTGTATGATGCGCTCG
1:	TrpAlaLysGlyArgPheThrIleSerArgThrSerThrThrValAspLeuLysIleThr
	TGGGCGAAAGGCCGATTCACCATCTCCAGAACCTCGACCACGGTGGATCTGAAAATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTCCGGCTAAGTGGTAGAGGTCTTGGAGCTGGTGCCACCTAGACTTTTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTyrGlyGlyAlaAsn
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTATGGTGGTGCTAAT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAATACCACCACGATTA
1:	TyrTyrGluHisPheAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	TATTATGAGCACTTTAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!----	354
	ATAATACTCGTGAAATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626S-E12 SEQ ID No. 5, 221, 222
1:	GlnThrValLysGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGACAGTGAAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCTGTCACTTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrValSerGlyPheSerLeuSerAsnTyrAlaMetThrTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAGTAACTATGCAATGACCTGGGTCCGCCAGGCTCCG
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTCATTGATACGTTACTGGACCCAGGCGGTCCGAGGC
1:	GlyLysGlyLeuGluTrpIleGlyIleIleSerSerGlyGlyTyrThrTyrTyrAlaSer
	GGGAAGGGGCTGGAATGGATCGGAATCATTAGTAGTGGTGGTTATACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTACCTAGCCTTAGTAATCATCACCACCAATATGTATGATGCGCTCG
1:	TrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuLysIleThr
	TGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACTTTTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTyrGlyGlyGlyAsn
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTATGGTGGTGGTAAC
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAATACCACCACCATTG
1:	TyrTyrGluHisTyrAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	TATTATGAGCACTATAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!----	354
	ATAATACTCGTGATATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-F7 SEQ ID No. 6, 223, 224
1:	GlnSerLeuGluGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCGACCTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrValSerGlyPheSerLeuSerAlaTyrThrMetThrTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAGTGCCTATACAATGACCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTCACGGATATGTTACTGGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTrpIleGlyAlaIleSerThrGlyGlySerThrTyrTyrAlaAsn
	GGGAAGGGGCTGGAATGGATCGGAGCCATTAGTACTGGTGGTAGCACATACTACGCGAAC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTACCTAGCCTCGGTAATCATGACCACCATCGTGTATGATGCGCTTG
1:	TrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuLysIleThr
	TGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACTTTTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTyrGlySerAsnAsn
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTATGGTAGTAATAAT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAATACCATCATTATTA
1:	TyrTyrGluHisPheLysIleTrpGlyProGlyThrLeuValThrValSerLeu
	TATTATGAGCACTTTAAGATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!----	354
	ATAATACTCGTGAAATTCTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-F5 SEQ ID No. 7, 225, 226
1:	GlnGluGlnLeuMetGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeu
	CAGGAGCAGCTGATGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTC
1	---------!---------!---------!---------!---------!---------!	60
	GTCCTCGTCGACTACCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAG
1:	ThrCysThrValSerGlyPheSerLeuSerSerTyrAlaMetThrTrpValArgGlnAla
	ACCTGCACAGTCTCTGGATTCTCCCTCAGTAGCTATGCAATGACCTGGGTCCGCCAGGCT
61	---------!---------!---------!---------!---------!---------!	120
	TGGACGTGTCAGAGACCTAAGAGGGAGTCATCGATACGTTACTGGACCCAGGCGGTCCGA
1:	ProGlyLysGlyLeuGluTrpIleGlyIleIleSerThrAsnGlyAsnThrTyrTyrAla
	CCAGGGAAGGGGCTGGAATGGATCGGAATCATTAGTACTAATGGTAACACATACTACGCG
121	---------!---------!---------!---------!---------!---------!	180
	GGTCCCTTCCCCGACCTTACCTAGCCTTAGTAATCATGATTACCATTGTGTATGATGCGC
1:	SerTrpAlaLysGlyArgPheAlaIleSerLysThrSerThrThrValAspLeuLysIle
	AGCTGGGCGAAAGGCCGATTCGCCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATC
181	---------!---------!---------!---------!---------!---------!	240
	TCGACCCGCTTTCCGGCTAAGCGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACTTTTAG
1:	ThrSerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTyrGlySerAsn
	ACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTATGGTAGTAAT
241	---------!---------!---------!---------!---------!---------!	300
	TGGTCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAATACCATCATTA
1:	AsnTyrTyrGluHisPheAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	AATTATTATGAGCACTTTAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!-------	357
	TTAATAATACTCGTGAAATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-C5 SEQ ID No. 8, 227, 228
1:	GlnGluGlnLeuLysGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeu
	CAGGAGCAGCTGAAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTC
1	---------!---------!---------!---------!---------!---------!	60
	GTCCTCGTCGACTTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAG
1:	ThrCysThrValSerGlyPheSerLeuSerAsnTyrAlaMetSerTrpValArgGlnAla
	ACCTGCACAGTCTCTGGATTCTCCCTCAGTAACTATGCAATGAGCTGGGTCCGCCAGGCT
61	---------!---------!---------!---------!---------!---------!	120
	TGGACGTGTCAGAGACCTAAGAGGGAGTCATTGATACGTTACTCGACCCAGGCGGTCCGA
1:	ProGlyLysGlyLeuGluTrpIleGlyIleIleSerSerSerGlyAsnThrTyrTyrAla
	CCAGGGAAGGGGCTGGAATGGATCGGAATCATTAGTAGTAGTGGTAACACATACTACGCG
121	---------!---------!---------!---------!---------!---------!	180
	GGTCCCTTCCCCGACCTTACCTAGCCTTAGTAATCATCATCACCATTGTGTATGATGCGC
1:	SerTrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuLysIle
	AGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATC
181	---------!---------!---------!---------!---------!---------!	240
	TCGACCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACTTTTAG
1:	ThrSerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTyrGlyTyrAsn
	ACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTATGGTTATAAT
241	---------!---------!---------!---------!---------!---------!	300
	TGGTCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAATACCAATATTA
1:	AsnTyrTyrGluHisPheAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	AATTATTATGAGCACTTTAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!-------	357
	TTAATAATACTCGTGAAATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626S-G9 SEQ ID No. 9, 229, 230
1:	GlnGluGlnLeuGluGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeu
	CAGGAGCAGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTC
1	---------!---------!---------!---------!---------!---------!	60
	GTCCTCGTCGACCTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAG
1:	ThrCysThrAlaSerGlyPheSerLeuSerAlaTyrSerMetSerTrpValArgGlnAla
	ACCTGCACAGCCTCTGGATTCTCCCTCAGTGCCTACTCCATGAGCTGGGTCCGCCAGGCT
61	---------!---------!---------!---------!---------!---------!	120
	TGGACGTGTCGGAGACCTAAGAGGGAGTCACGGATGAGGTACTCGACCCAGGCGGTCCGA
1:	ProGlyLysGlyLeuGluTrpIleGlyIleIleSerSerSerGlyTyrThrTyrTyrAla
	CCAGGGAAGGGGCTGGAATGGATCGGAATCATTAGTAGCAGTGGTTACACATACTACGCG
121	---------!---------!---------!---------!---------!---------!	180
	GGTCCCTTCCCCGACCTTACCTAGCCTTAGTAATCATCGTCACCAATGTGTATGATGCGC
1:	SerTrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuGluIle
	AGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGGAGATC
181	---------!---------!---------!---------!---------!---------!	240
	TCGACCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACCTCTAG
1:	ThrSerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTyrGlyTyrAsn
	ACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTATGGTTATAAT
241	---------!---------!---------!---------!---------!---------!	300
	TGGTCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAATACCAATATTA
1:	AsnTyrTyrGluHisPheAsnMetTrpGlyProGlyThrLeuValThrValSerLeu
	AATTATTATGAGCACTTTAACATGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!-------	357
	TTAATAATACTCGTGAAATTGTACACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626S-F8 SEQ ID No. 10, 231, 232
1:	GlnSerValLysGluSerGluGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGTCAGTGAAGGAGTCCGAGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGTCACTTCCTCAGGCTCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrValAlaGlyPheSerLeuSerHisTyrHisMetSerTrpValArgGlnAlaPro
	TGCACAGTCGCTGGATTCTCCCTCAGCCACTACCATATGAGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGCGACCTAAGAGGGAGTCGGTGATGGTATACTCGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTrpIleGlyIleIleGlySerSerGlyAsnThrTrpTyrAlaSer
	GGGAAGGGGCTGGAATGGATCGGAATCATTGGTAGTAGTGGAAACACATGGTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTACCTAGCCTTAGTAACCATCATCACCTTTGTGTACCATGCGCTCG
1:	TrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuArgIleThr
	TGGGCGAAAGGCCGATTCACCATCTCCAAGACCTCGACCACGGTGGATCTGAGAATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTCCGGCTAAGTGGTAGAGGTTCTGGAGCTGGTGCCACCTAGACTCTTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgAlaGlyAlaSerAsnAsn
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGCTGGTGCTAGTAACAAT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCGACCACGATCATTGTTA
1:	TyrTyrAsnTyrPheAsnValTrpGlyProGlyThrLeuValThrValSerLeu
	TATTATAATTACTTTAACGTCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!----	354
	ATAATATTAATGAAATTGCAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-F10 SEQ ID No. 11, 233, 234
1:	GlnSerValLysGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGTCGGTGAAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCCACTTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrValAlaGlyPheSerLeuSerArgTyrTyrMetSerTrpValArgGlnAlaPro
	TGCACAGTCGCTGGATTCTCCCTCAGCCGCTACTATATGAGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGCGACCTAAGAGGGAGTCGGCGATGATATACTCGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTrpIleGlyIleIleSerSerSerGlySerThrTyrTyrAlaSer
	GGGAAGGGGCTGGAATGGATCGGAATCATTAGTAGTAGTGGTAGCACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTACCTAGCCTTAGTAATCATCATCACCATCGTGTATGATGCGCTCG
1:	TrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuArgIleThr
	TGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAGAATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACTCTTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyGlyAlaSerAsnAsn
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTGGTGCTAGTAATAAT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCACCACGATCATTATTA
1:	TyrTyrAsnTyrPheAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	TATTATAATTACTTTAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!----	354
	ATAATATTAATGAAATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-G12 SEQ ID No. 12, 235, 236
1:	GlnSerLeuGluGluSerGlyGlyGlyLeuPheLysProThrAspThrLeuThrLeuThr
	CAGTCGTTGGAGGAGTCCGGGGGAGGTCTCTTCAAGCCAACGGATACCCTGACTCTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCAACCTCCTCAGGCCCCCTCCAGAGAAGTTCGGTTGCCTATGGGACTGAGAGTGG
1:	CysThrValSerGlyPheProLeuSerThrTyrGlyIleThrTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCCCCCTCAGTACCTATGGAATAACCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGGGGGAGTCATGGATACCTTATTGGACCCAGGCGGTCCGAGGT
1:	GlyAsnGlyLeuGluTrpIleGlyIleIleSerSerGlyGlySerThrHisTyrAlaSer
	GGGAACGGGCTGGAATGGATCGGAATCATTAGTAGTGGTGGTAGCACACACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTGCCCGACCTTACCTAGCCTTAGTAATCATCACCACCATCGTGTGTGATGCGCTCG
1:	TrpAlaLysSerArgSerThrIleThrArgAspThrAsnGluAsnThrValThrLeuLys
	TGGGCGAAAAGCCGATCCACCATCACCAGAGACACCAACGAGAACACGGTGACTCTGAAA
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTTCGGCTAGGTGGTAGTGGTCTCTGTGGTTGCTCTTGTGCCACTGAGACTTT
1:	MetThrSerLeuThrValAlaAspThrAlaThrTyrPheCysAlaArgAlaProTyrPhe
	ATGACCAGTCTGACAGTCGCGGACACGGCCACCTATTTCTGTGCGAGAGCCCCCTACTTT
241	---------!---------!---------!---------!---------!---------!	300
	TACTGGTCAGACTGTCAGCGCCTGTGCCGGTGGATAAAGACACGCTCTCGGGGGATGAAA
1:	ArgTrpAspPheAsnTrpAspLeuSerAlaPheAspProTrpGlyProGlyThrLeuVal
	AGGTGGGATTTTAATTGGGATCTTTCCGCTTTTGATCCCTGGGGCCCAGGCACCCTGGTC
301	---------!---------!---------!---------!---------!---------!	360
	TCCACCCTAAAATTAACCCTAGAAAGGCGAAAACTAGGGACCCCGGGTCCGTGGGACCAG
1:	ThrValSerSer
	ACCGTCTCCTCA
361	---------!--	372
	TGGCAGAGGAGT
21626B-A11 SEQ ID No. 13, 237, 238
1:	GlnSerLeuGlyGluSerGlyGlyArgLeuValLysProAspGluThrLeuThrLeuThr
	CAGTCGCTGGGGGAGTCCGGGGGTCGCCTGGTCAAGCCTGACGAAACCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCGACCCCCTCAGGCCCCCAGCGGACCAGTTCGGACTGCTTTGGGACTGTGAGTGG
1:	CysThrAlaSerGlyPheSerLeuSerAsnTyrAspMetGlyTrpValArgGlnAlaPro
	TGCACAGCCTCTGGATTCTCCCTCAGTAACTACGACATGGGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCGGAGACCTAAGAGGGAGTCATTGATGCTGTACCCGACCCAGGCGGTCCGAGGT
1:	GlyGluGlyLeuGluTyrIleGlyTrpIleThrThrGlyGlySerAlaTyrTyrAlaAsn
	GGGGAGGGGCTGGAATATATCGGATGGATTACTACTGGTGGTAGCGCATACTACGCGAAC
121	---------!---------!---------!---------!---------!---------!	180
	CCCCTCCCCGACCTTATATAGCCTACCTAATGATGACCACCATCGCGTATGATGCGCTTG
1:	TrpAlaLysGlyArgPheThrIleSerArgThrSerThrThrValAspLeuLysIleSer
	TGGGCAAAAGGCCGATTCACCATCTCCAGAACCTCGACCACGGTGGATCTGAAAATCAGC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGTTTTCCGGCTAAGTGGTAGAGGTCTTGGAGCTGGTGCCACCTAGACTTTTAGTCG
1:	SerProThrSerGluAspThrAlaThrTyrPheCysAlaArgAspGlyGlyArgGlyTyr
	AGTCCGACAAGTGAGGACACGGCCACCTATTTCTGTGCCAGAGATGGTGGCCGTGGTTAT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTCACTCCTGTGCCGGTGGATAAAGACACGGTCTCTACCACCGGCACCAATA
1:	GlyTyrSerPheSerIleTrpGlyProGlyThrLeuValThrValSerSer
	GGTTATTCATTTAGCATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCA
301	---------!---------!---------!---------!---------!-	351
	CCAATAAGTAAATCGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAGT
21626B-B5 SEQ ID No. 14, 239, 240
1:	GlnThrValLysGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGACGGTGAAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCTGCCACTTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrAlaSerGlyPheSerPheSerGlyTrpSerValThrTrpValArgGInAlaPro
	TGCACAGCCTCTGGATTCTCCTTCAGTGGCTGGTCGGTGACCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCGGAGACCTAAGAGGAAGTCACCGACCAGCCACTGGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTrpIleGlyTyrIleTyrProArgSerGlySerThrAsnTyrAla
	GGGAAGGGGCTGGAGTGGATCGGATACATTTATCCTCGGAGTGGTAGCACAAACTACGCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTCACCTAGCCTATGTAAATAGGAGCCTCACCATCGTGTTTGATGCGC
1:	ArgTrpValArgGlyArgPheThrIleSerAlaThrSerThrThrValAspLeuLysLeu
	AGGTGGGTGAGAGGCCGATTCACCATCTCCGCAACCTCGACCACGGTGGATCTGAAACTC
181	---------!---------!---------!---------!---------!---------!	240
	TCCACCCACTCTCCGGCTAAGTGGTAGAGGCGTTGGAGCTGGTGCCACCTAGACTTTGAG
1:	ThrSerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyGlyTyrGlyGly
	ACCAGTCCGACAACCGAGGACACGGCCACTTATTTCTGTGCCAGAGGAGGTTACGGTGGT
241	---------!---------!---------!---------!---------!---------!	300
	TGGTCAGGCTGTTGGCTCCTGTGCCGGTGAATAAAGACACGGTCTCCTCCAATGCCACCA
1:	IleAspTrpGlySerMetAspIleTrpGlyProGlyThrLeuValThrValSerLeu
	ATTGACTGGGGTAGCATGGACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!-------	357
	TAACTGACCCCATCGTACCTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-C2 SEQ ID No. 15, 241, 242
1:	GlnThrValLysGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGACAGTGAAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCTGTCACTTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrAlaSerGlyPheSerLeuAsnSerAspAspMetThrTrpValArgGlnAlaPro
	TGCACAGCCTCTGGATTCTCCCTCAACAGCGACGACATGACCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCGGAGACCTAAGAGGGAGTTGTCGCTGCTGTACTGGACCCAGGCGGTCCGAGGT
1:	GlyMetGlyLeuGluTrpIleGlyThrMetHisAlaSerGlyPheThrTyrTyrAlaSer
	GGGATGGGGCTGGAATGGATTGGAACCATGCATGCTAGCGGTTTCACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTACCCCGACCTTACCTAACCTTGGTACGTACGATCGCCAAAGTGTATGATGCGCTCG
1:	TrpAlaGlnGlyArgPheThrIleSerGlyThrSerThrThrValAspLeuLysIleThr
	TGGGCGCAAGGCCGATTCACCATCTCCGGAACCTCGACCACGGTGGATCTGAAAATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCGTTCCGGCTAAGTGGTAGAGGCCTTGGAGCTGGTGCCACCTAGACTTTTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyAlaProGlyTyrThr
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTGCTCCTGGTTATACT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCACGAGGACCAATATGA
1:	IleAspAsnIleTrpGlyProGlyThrLeuValThrValSerLeu
	ATTGATAACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!-----	345
	TAACTATTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-H4 SEQ ID No. 16, 243, 244
1:	GlnSerLeuGluGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGTCGTTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCAACCTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrValSerGlyPheSerLeuSerAspHisAlaMetIleTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAGTGACCATGCAATGATCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTCACTGGTACGTTACTAGACCCAGGCGGTCCGAGGT
1:	GlyGluGlyLeuGluTrpValGlyIleIleTyrProSerGlySerThrTyrTyrAlaAsn
	GGCGAGGGGCTGGAATGGGTCGGGATCATTTATCCTAGTGGTAGCACATACTACGCGAAC
121	---------!---------!---------!---------!---------!---------!	180
	CCGCTCCCCGACCTTACCCAGCCCTAGTAAATAGGATCACCATCGTGTATGATGCGCTTG
1:	GlyAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuLysMetThr
	GGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGAAAATGACC
181	---------!---------!---------!---------!---------!---------!	240
	CCCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACTTTTACTGG
1:	SerLeuIleIleGluAspThrAlaThrTyrPheCysAlaArgAspTyrAspSerGlyTrp
	AGCCTGATAATCGAGGACACGGCCACGTATTTCTGTGCCAGAGACTATGATAGTGGCTGG
241	---------!---------!---------!---------!---------!---------!	300
	TCGGACTATTAGCTCCTGTGCCGGTGCATAAAGACACGGTCTCTGATACTATCACCGACC
1:	GlyAlaAspIleTrpGlyProGlyThrProValThrValSerLeu
	GGTGCGGATATCTGGGGCCCAGGCACCCCGGTCACCGTCTCCTTG
301	---------!---------!---------!---------!-----	345
	CCACGCCTATAGACCCCGGGTCCGTGGGGCCAGTGGCAGAGGAAC
21626B-C8 SEQ ID No. 17, 245, 246
1:	GlnThrValLysGluSerGluGlyGlyLeuPheLysProThrAspThrLeuThrLeuThr
	CAGACAGTGAAGGAGTCCGAGGGAGGTCTCTTCAAGCCAACGGATACCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCTGTCACTTCCTCAGGCTCCCTCCAGAGAAGTTCGGTTGCCTATGGGACTGTGAGTGG
1:	CysThrValSerGlyPheSerLeuSerIleTyrGlyValSerTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAGTATCTATGGAGTGAGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTCATAGATACCTCACTCGACCCAGGCGGTCCGAGGT
1:	GlyAsnGlyLeuGluTrpIleGlySerIleSerAlaThrGlyIleThrTyrTyrAlaSer
	GGGAACGGGCTGGAATGGATCGGGTCCATTAGTGCTACTGGTATCACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTGCCCGACCTTACCTAGCCCAGGTAATCACGATGACCATAGTGTATGATGCGCTCG
1:	TrpAlaLysSerArgSerThrValThrArgAsnThrAsnLeuAsnThrValThrLeuLys
	TGGGCGAAAAGCCGATCCACCGTCACCAGAAACACCAACCTGAACACGGTGACTCTGAAA
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTTCGGCTAGGTGGCAGTGGTCTTTGTGGTTGGACTTGTGCCACTGAGACTTT
1:	MetThrSerLeuThrAlaAlaAspThrAlaThrTyrPheCysThrArgGlyHisThrTyr
	ATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTACTAGAGGTCATACTTAT
241	---------!---------!---------!---------!---------!---------!	300
	TACTGGTCAGACTGTCGGCGCCTGTGCCGGTGGATAAAGACATGATCTCCAGTATGAATA
1:	SerThrProAspIleTrpGlyProGlyThrLeuValThrValSerSer
	TCTACCCCTGACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCA
301	---------!---------!---------!---------!--------	348
	AGATGGGGACTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAGT
21626B-E6 SEQ ID No. 18, 247, 248
1:	GlnSerLeuGluGluSerGlyGlyGlyLeuIleLysProThrAspThrLeuThrLeuThr
	CAGTCGCTGGAGGAGTCCGGGGGAGGCCTGATCAAGCCAACGGATACCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCGACCTCCTCAGGCCCCCTCCGGACTAGTTCGGTTGCCTATGGGACTGTGAGTGG
1:	CysThrValSerGlyPheSerLeuSerArgTyrGlyValIleTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAGTAGGTATGGAGTGATCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTCATCCATACCTCACTAGACCCAGGCGGTCCGAGGT
1:	GlySerGlyLeuGluTrpIleGlyAlaIleThrAlaThrGlyIleThrTyrTyrAlaSer
	GGGAGTGGCCTGGAATGGATCGGAGCCATTACTGCTACTGGTATCACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTCACCGGACCTTACCTAGCCTCGGTAATGACGATGACCATAGTGTATGATGCGCTCG
1:	TrpAlaLysSerArgSerThrIleThrArgAsnThrAsnLeuAsnThrValThrLeuLys
	TGGGCGAAAAGCCGATCCACCATCACCAGAAACACCAACCTGAACACGGTGACTCTGAAA
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTTCGGCTAGGTGGTAGTGGTCTTTGTGGTTGGACTTGTGCCACTGAGACTTT
1:	MetThrSerLeuThrAlaAlaAspThrAlaThrTyrPheCysAlaGlyGlyHisThrPhe
	ATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGGGGGGTCATACTTTT
241	---------!---------!---------!---------!---------!---------!	300
	TACTGGTCAGACTGTCGGCGCCTGTGCCGGTGGATAAAGACACGCCCCCCAGTATGAAAA
1:	SerThrAspValGlyAspIleTrpGlyProGlyThrProValThrValSerSer
	AGTACTGATGTCGGGGACATCTGGGGCCCAGGCACCCCGGTCACCGTCTCCTCA
301	---------!---------!---------!---------!---------!----	354
	TCATGACTACAGCCCCTGTAGACCCCGGGTCCGTGGGGCCAGTGGCAGAGGAGT
21626B-G5 SEQ ID No. 19, 249, 250
1:	GlnSerValLysGluSerGluGlyGlyLeuPheLysProAlaAspThrLeuThrLeuThr
	CAGTCGGTGAAGGAGTCCGAGGGAGGTCTCTTCAAGCCAGCGGATACCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCCACTTCCTCAGGCTCCCTCCAGAGAAGTTCGGTCGCCTATGGGACTGTGAGTGG
1:	CysThrValSerGlyPheSerLeuAsnSerTyrThrIleSerTrpValArgGlnAlaPro
	TGCACAGTCTCTGGATTCTCCCTCAATAGCTATACAATAAGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCAGAGACCTAAGAGGGAGTTATCGATATGTTATTCGACCCAGGCGGTCCGAGGT
1:	GlyAsnGlyLeuGluTrpIleGlyIleIleAsnThrTyrGlyThrThrAsnTyrAlaSer
	GGGAACGGGCTGGAATGGATCGGAATCATTAATACTTATGGTACCACTAACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTGCCCGACCTTACCTAGCCTTAGTAATTATGAATACCATGGTGATTGATGCGCTCG
1:	TrpAlaLysSerArgSerThrIleThrArgAsnThrAsnGluAsnThrValThrLeuLys
	TGGGCGAAAAGCCGATCCACCATCACCAGAAACACCAACGAGAACACGGTGACTCTGAAA
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTTTCGGCTAGGTGGTAGTGGTCTTTGTGGTTGCTCTTGTGCCACTGAGACTTT
1:	MetThrSerLeuThrAlaAlaAspThrAlaThrTyrPheCysAlaSerLeuTyrThrThr
	ATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGCTTGTATACAACA
241	---------!---------!---------!---------!---------!---------!	300
	TACTGGTCAGACTGTCGGCGCCTGTGCCGGTGGATAAAGACACGCTCGAACATATGTTGT
1:	GlnThrAsnIleTrpGlyProGlyThrLeuValThrValSerSer
	CAGACTAACATTTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCA
301	---------!---------!---------!---------!-----	345
	GTCTGATTGTAAACCCCGGGTCCGTGGGACCAGTGGCAGAGGAGT
21626B-H3 SEQ ID No. 20, 251, 252
1:	GlnSerLeuGlyGluSerArgGlyArgLeuValThrProGlyGlySerLeuThrLeuThr
	CAGTCGCTGGGGGAGTCCAGGGGTCGCCTGGTAACGCCTGGAGGATCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCGACCCCCTCAGGTCCCCAGCGGACCATTGCGGACCTCCTAGGGACTGTGAGTGG
1:	CysThrAlaSerGlyPheSerLeuSerSerTyrAlaMetGlyTrpValArgGlnAlaPro
	TGCACAGCCTCTGGATTCTCCCTCAGTAGCTATGCAATGGGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCGGAGACCTAAGAGGGAGTCATCGATACGTTACCCGACCCAGGCGGTCCGAGGT
1:	GlyLysGlyLeuGluTyrIleGlyTrpIleSerAlaGlyGlyThrThrTyrTyrAlaSer
	GGGAAGGGGCTGGAATACATCGGATGGATTAGTGCTGGTGGTACCACATACTACGCGAGC
121	---------!---------!---------!---------!---------!---------!	180
	CCCTTCCCCGACCTTATGTAGCCTACCTAATCACGACCACCATGGTGTATGATGCGCTCG
1:	TrpValAsnSerArgPheThrIleSerArgThrSerThrThrValAspLeuGluMetThr
	TGGGTGAATAGTCGATTCACCATCTCCAGAACCTCGACCACGGTGGATCTGGAAATGACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCACTTATCAGCTAAGTGGTAGAGGTCTTGGAGCTGGTGCCACCTAGACCTTTACTGG
1:	SerLeuThrThrGluAspThrAlaThrTyrPheCysAlaArgGluGlyThrGlyTrpGly
	AGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGAGGGTACTGGCTGGGGT
241	---------!---------!---------!---------!---------!---------!	300
	TCAGACTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCTCCCATGACCGACCCCA
1:	AlaTyrAspIleTrpGlyProGlyThrLeuValThrValSerLeu
	GCCTATGACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!-----	345
	CGGATACTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-A8 SEQ ID No. 21, 253, 254
1:	GlnLeuGluGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThrCys
	CAGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGC
1	---------!---------!---------!---------!---------!---------!	60
	GTCGACCTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGGACG
1:	ThrValSerGlyIleAspLeuSerSerAspSerIleGlyTrpValArgGlnAlaProGly
	ACCGTCTCTGGAATCGACCTCAGTAGCGACAGTATTGGCTGGGTCCGCCAGGCTCCAGGG
61	---------!---------!---------!---------!---------!---------!	120
	TGGCAGAGACCTTAGCTGGAGTCATCGCTGTCATAACCGACCCAGGCGGTCCGAGGTCCC
1:	LysGlyLeuGluTrpIleGlyIleIleTyrProSerGlyAsnValTyrTyrAlaSerTrp
	AAGGGGCTGGAATGGATCGGAATCATTTATCCTAGTGGTAATGTATACTACGCGAGCTGG
121	---------!---------!---------!---------!---------!---------!	180
	TTCCCCGACCTTACCTAGCCTTAGTAAATAGGATCACCATTACATATGATGCGCTCGACC
1:	AlaLysGlyArgLeuThrIleSerLysThrSerThrThrValGluLeuLysMetThrSer
	GCGAAAGGCCGACTCACCATCTCCAAAACCTCGACCACGGTGGAGCTGAAAATGACCAGT
181	---------!---------!---------!---------!---------!---------!	240
	CGCTTTCCGGCTGAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTCGACTTTTACTGGTCA
1:	LeuThrThrGluAspThrAlaThrTyrPheCysAlaArgAspTyrTyrSerThrThrLeu
	CTGACAACCGAGGACACGGCCACCTATTTTTGTGCCAGAGATTACTATAGTACTACCTTA
241	---------!---------!---------!---------!---------!---------!	300
	GACTGTTGGCTCCTGTGCCGGTGGATAAAAACACGGTCTCTAATGATATCATGATGGAAT
1:	AspIleTrpGlyProGlyThrLeuValThrValSerLeu
	GACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTG
301	---------!---------!---------!---------	339
	CTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAC
21626B-D1 SEQ ID No. 22, 255, 256
1:	GlnGluGlnLeuLysGluSerArgGlyArgLeuValThrProGlyGlySerLeuThrLeu
	CAGGAGCAGCTGAAGGAGTCCCGGGGTCGCCTGGTAACGCCTGGAGGATCCCTGACACTC
1	---------!---------!---------!---------!---------!---------!	60
	GTCCTCGTCGACTTCCTCAGGGCCCCAGCGGACCATTGCGGACCTCCTAGGGACTGTGAG
1:	ThrCysThrValSerGlyIleAspLeuSerSerAsnAlaMetSerTrpValArgGlnAla
	ACCTGCACAGTCTCTGGAATCGACCTCAGTAGCAATGCAATGAGCTGGGTCCGCCAGGCT
61	---------!---------!---------!---------!---------!---------!	120
	TGGACGTGTCAGAGACCTTAGCTGGAGTCATCGTTACGTTACTCGACCCAGGCGGTCCGA
1:	ProGlyGluGlyLeuGluTrpIleGlyThrIleSerGlyGlySerGlySerThrTrpTyr
	CCAGGGGAGGGGCTGGAATGGATCGGAACCATTAGTGGTGGTAGTGGTAGCACATGGTAC
121	---------!---------!---------!---------!---------!---------!	180
	GGTCCCCTCCCCGACCTTACCTAGCCTTGGTAATCACCACCATCACCATCGTGTACCATG
1:	AlaSerTrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValTyrLeuLys
	GCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAGACCTCGACCACGGTGTATCTGAAA
181	---------!---------!---------!---------!---------!---------!	240
	CGCTCGACCCGCTTTCCGGCTAAGTGGTAGAGGTTCTGGAGCTGGTGCCACATAGACTTT
1:	MetThrSerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTrpAspGly
	ATGACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTGGGACGGC
241	---------!---------!---------!---------!---------!---------!	300
	TACTGGTCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAACCCTGCCG
1:	PheSerThrTrpGlyProGlyThrLeuValThrValSerLeu
	TTTAGCACCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!--	342
	AAATCGTGGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-G1 SEQ ID No. 23, 257, 258
1:	GlnGluGlnLeuValGluSerGlyGlyArgLeuValThrProGlySerProLeuThrLeu
	CAGGAGCAGCTGGTGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGTCACCCCTGACACTC
1	---------!---------!---------!---------!---------!---------!	60
	GTCCTCGTCGACCACCTCAGGCCCCCAGCGGACCAGTGCGGACCCAGTGGGGACTGTGAG
1:	ThrCysThrValSerGlyPheSerLeuSerSerTyrTrpMetSerTrpValArgGlnAla
	ACCTGCACAGTCTCTGGATTCTCCCTCAGTAGCTACTGGATGAGCTGGGTCCGCCAAGCT
61	---------!---------!---------!---------!---------!---------!	120
	TGGACGTGTCAGAGACCTAAGAGGGAGTCATCGATGACCTACTCGACCCAGGCGGTTCGA
1:	ProGlyLysGlyLeuGluTrpMetGlyAspIleSerAsnThrGlyLysIleTyrTyrAla
	CCAGGGAAGGGGCTGGAGTGGATGGGAGATATTAGTAATACTGGTAAGATATATTACGCG
121	---------!---------!---------!---------!---------!---------!	180
	GGTCCCTTCCCCGACCTCACCTACCCTCTATAATCATTATGACCATTCTATATAATGCGC
1:	AsnTrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuThrIle
	AACTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGACAATC
181	---------!---------!---------!---------!---------!---------!	240
	TTGACCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACTGTTAG
1:	ThrSerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyMetAsnValTyr
	ACCAGTCCGACAACGGAGGACACGGCCACCTATTTCTGTGCCAGAGGTATGAATGTTTAT
241	---------!---------!---------!---------!---------!---------!	300
	TGGTCAGGCTGTTGCCTCCTGTGCCGGTGGATAAAGACACGGTCTCCATACTTACAAATA
1:	AspIleTrpGlyProGlyThrLeuValThrValSerLeu
	GACATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------	339
	CTGTAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626B-C4-8 SEQ ID No. 24, 259, 260
1:	GlnSerLeuGluGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeuThr
	CAGTCGTTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC
1	---------!---------!---------!---------!---------!---------!	60
	GTCAGCAACCTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAGTGG
1:	CysThrAlaSerGlyPheSerLeuSerSerTyrTyrMetSerTrpValArgGlnAlaPro
	TGCACAGCCTCTGGATTCTCCCTCAGTAGCTACTACATGAGCTGGGTCCGCCAGGCTCCA
61	---------!---------!---------!---------!---------!---------!	120
	ACGTGTCGGAGACCTAAGAGGGAGTCATCGATGATGTACTCGACCCAGGCGGTCCGAGGT
1:	GluLysGlyLeuGluTrpIleGlyIleIleTyrProSerGlyAsnThrTyrTyrAlaAsn
	GAAAAGGGGCTGGAATGGATCGGAATCATTTATCCTAGTGGTAACACATACTACGCGAAC
121	---------!---------!---------!---------!---------!---------!	180
	CTTTTCCCCGACCTTACCTAGCCTTAGTAAATAGGATCACCATTGTGTATGATGCGCTTG
1:	TrpAlaAsnGlyArgPheAlaIleSerArgThrSerThrThrValAspLeuLysIleThr
	TGGGCGAATGGTCGATTCGCCATCTCCAGAACCTCGACCACGGTGGATCTGAAGATCACC
181	---------!---------!---------!---------!---------!---------!	240
	ACCCGCTTACCAGCTAAGCGGTAGAGGTCTTGGAGCTGGTGCCACCTAGACTTCTAGTGG
1:	SerProThrThrGluAspThrAlaThrTyrPheCysAlaArgAspSerGlyTyrProAsp
	AGTCCGACAACCGAGGACACGGCCACCTATTTCTGCGCCAGAGATTCTGGTTATCCTGAC
241	---------!---------!---------!---------!---------!---------!	300
	TCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACGCGGTCTCTAAGACCAATAGGACTG
1:	IleTrpGlyProGlyThrLeuValThrValSerLeu
	ATCTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!------	339
	TAGACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT
21626S-A1 SEQ ID No. 25, 261, 262
1:	GlnGluGlnLeuLysGluSerGlyGlyArgLeuValThrProGlyThrProLeuThrLeu
	CAGGAGCAGCTGAAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTC
1	---------!---------!---------!---------!---------!---------!	60
	GTCCTCGTCGACTTCCTCAGGCCCCCAGCGGACCAGTGCGGACCCTGTGGGGACTGTGAG
1:	ThrCysThrAlaSerGlyPheSerLeuSerAlaTyrSerMetSerTrpValArgGlnAla
	ACCTGCACAGCCTCTGGATTCTCCCTCAGTGCCTACTCCATGAGCTGGGTCCGCCAGGCT
61	---------!---------!---------!---------!---------!---------!	120
	TGGACGTGTCGGAGACCTAAGAGGGAGTCACGGATGAGGTACTCGACCCAGGCGGTCCGA
1:	ProGlyLysGlyLeuGluTrpIleGlyIleIleSerSerSerGlyTyrThrTyrTyrAla
	CCAGGGAAGGGGCTGGAATGGATCGGAATCATTAGTAGCAGTGGTTACACATACTACGCG
121	---------!---------!---------!---------!---------!---------!	180
	GGTCCCTTCCCCGACCTTACCTAGCCTTAGTAATCATCGTCACCAATGTGTATGATGCGC
1:	SerTrpAlaLysGlyArgPheThrIleSerLysThrSerThrThrValAspLeuGluIle
	AGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTGGAGATC
181	---------!---------!---------!---------!---------!---------!	240
	TCGACCCGCTTTCCGGCTAAGTGGTAGAGGTTTTGGAGCTGGTGCCACCTAGACCTCTAG
1:	ThrSerProThrThrGluAspThrAlaThrTyrPheCysAlaArgGlyTyrGlyTyrAsn
	ACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGTTATGGTTATAAT
241	---------!---------!---------!---------!---------!---------!	300
	TGGTCAGGCTGTTGGCTCCTGTGCCGGTGGATAAAGACACGGTCTCCAATACCAATATTA
1:	AsnTyrTyrGluHisPheAsnMetTrpGlyProGlyThrLeuValThrValSerLeu
	AATTATTATGAGCACTTTAACATGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTTA
301	---------!---------!---------!---------!---------!-------	357
	TTAATAATACTCGTGAAATTGTACACCCCGGGTCCGTGGGACCAGTGGCAGAGGAAT

Light Chain Sequences

Listed below are light chain sequences of certain non-limiting anti-IgE antibodies, identified by name (e.g. “21626S-D5”) and ID number (e.g. “SEQ ID No. 26”).

21626S-D5 SEQ ID No. 26, 263, 264
1:	AlaGlnValMetAlaGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GCCCAAGTGATGGCCCAGACTCCAGCCTCCGTGTCTGAACCTGTCGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGTTCACTACCGGGTCTGAGGTCGGAGGCACAGACTTGGACAGCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnArgProSerLeuLeuIleTyrAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCTCGCTCCTGATCTATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGAGCGAGGACTAGATACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTACTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATGATACCATCGGCAATACGACCTCCC
1:	SerAlaPheGlyGlyGlyThrGluValValValLys
	AGTGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TCACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-B9 SEQ ID No. 27, 265, 266
1:	AlaIleAspLeuThrGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GCCATCGATCTGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGTAGCTAGACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCCTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-H8 SEQ ID No. 28, 265, 266
1:	AspGlyValMetThrGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GATGGTGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTACCACACTACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCCTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCCGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGGCCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626S-E6 SEQ ID No. 29, 269, 270
1:	AspValValMetThrGlnThrProAlaSerAlaSerGluProValGlyGlyThrValThr
	GATGTTGTGATGACCCAGACTCCAGCCTCCGCGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTACAACACTACTGGGTCTGAGGTCGGAGGCGCAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCCTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626S-E12 SEQ ID No. 30, 269, 270
1:	AspGlyValMetThrGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GATGGTGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTACCACACTACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnArgProSerLeuLeuIleTyrAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCTCGCTCCTGATCTATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGAGCGAGGACTAGATACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTACTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATGATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-F7 SEQ ID No. 31, 273, 274
1:	AspValValMetThrGlnThrProSerSerValSerGluProValGlyGlyThrValThr
	GATGTCGTGATGACCCAGACTCCGTCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTACAGCACTACTGGGTCTGAGGCAGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnArgProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlyIleArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCATTAGATCCGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTAATCTAGGCCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlyAsnArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAACCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATTGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-F5 SEQ ID No. 32, 275, 276
1:	AspGlyValMetThrGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GATGGCGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTACCGCACTACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCCTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-C5 SEQ ID No. 33, 275, 276
1:	AlaGlnGlyMetThrGlnThrProSerSerValSerGluProValGlyGlyThrValThr
	GCCCAAGGGATGACCCAGACTCCATCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGTTCCCTACTGGGTCTGAGGTAGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnArgProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlyIleArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCATTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTAATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlyAsnArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAACCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATTGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626S-G9 SEQ ID No. 34, 275, 276
1:	AlaGlnGlyMetThrGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GCCCAAGGGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGTTCCCTACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCCTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626S-F8 SEQ ID No. 35, 275, 276
1:	AspValValMetThrGlnThrProAlaSerValSerGluProValGlyGlyThrAlaThr
	GATGTTGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGCCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTACAACACTACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCGGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuMetHisAspValSerThrLeuAlaSerGlyValSerSer
	GGGCAGCCTCCCAAGCTCCTGATGCATGATGTATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTCGAGGACTACGTACTACATAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluPheThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTTCACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCAAGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-F10 SEQ ID No. 36, 283, 284
1:	AlaAlaValMetThrGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GCAGCCGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGTCGGCACTACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleHisAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCCTCCCAAGCTCCTGATCCATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTCGAGGACTAGGTACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTATTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATAATACCATCGGCAATACGACCTCCC
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-G12 SEQ ID No. 37, 283, 284
1:	AlaGlnValLeuThrGlnThrProAlaSerValSerAlaAlaValGlyGlyThrValThr
	GCCCAAGTGCTGACCCAGACTCCAGCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGTTCACGACTGGGTCTGAGGTCGGAGGCACAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleSerCysGlnSerSerGluSerValTyrLysAsnAsnTyrLeuSerTrpTyrGlnGln
	ATCAGTTGCCAGTCCAGTGAGAGTGTTTATAAGAACAACTACTTATCCTGGTATCAGCAG
61	---------!---------!---------!---------!---------!---------!	120
	TAGTCAACGGTCAGGTCACTCTCACAAATATTCTTGTTGATGAATAGGACCATAGTCGTC
1:	LysProGlyGlnProProLysGlyLeuIleTyrLeuSerSerThrLeuAlaSerGlyVal
	AAACCAGGGCAGCCTCCCAAAGGCCTGATCTATCTTTCATCCACTCTGGCATCTGGGGTC
121	---------!---------!---------!---------!---------!---------!	180
	TTTGGTCCCGTCGGAGGGTTTCCGGACTAGATAGAAAGTAGGTGAGACCGTAGACCCCAG
1:	ProSerArgPheSerGlySerGlySerGlyThrGlnPheThrLeuThrIleSerAspLeu
	CCATCGCGGTTCAGCGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTG
181	---------!---------!---------!---------!---------!---------!	240
	GGTAGCGCCAAGTCGCCGTCACCTAGACCCTGTGTCAAGTGAGAGTGGTAGTCGCTGGAC
1:	GluCysSerAspAlaAlaThrTyrTyrCysAlaGlyGlyTyrSerGlyAsnIleGlyAla
	GAGTGTAGCGATGCTGCCACTTACTACTGTGCAGGCGGTTATAGTGGTAATATTGGCGCT
241	---------!---------!---------!---------!---------!---------!	300
	CTCACATCGCTACGACGGTGAATGATGACACGTCCGCCAATATCACCATTATAACCGCGA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	AAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-A11 SEQ ID No. 38, 287, 288
1:	AlaLeuValMetThrGlnThrProAlaSerValGluAlaAlaValGlyGlyThrValThr
	GCGCTGGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGCGACCACTACTGGGTCTGAGGTCGGAGGCACCTCCGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnAsnIleGlyAsnTyrLeuSerTrpPheGlnGlnLysPro
	ATCAATTGCCAGGCCAGCCAGAACATTGGTAATTACTTATCCTGGTTTCAACAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCGGTCTTGTAACCATTAATGAATAGGACCAAAGTTGTCTTTGGT
1:	GlyGlnArgProLysLeuLeuIleTyrLysAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCAAGCTCCTGATCTACAAGGCTTCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGTTCGAGGACTAGATGTTCCGAAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerGlySerGlyThrGlnPheThrLeuThrIleSerGlyValGluCys
	CGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGGCGTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCACCTAGACCCTGTGTCAAGTGAGAGTGGTAGTCGCCGCACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleAsnValAspAsnThr
	GCCGATGCTGCCACTTACTACTGTCAACAAGATGCTGCTGTTATTAATGTTGATAATACT
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTTGTTCTACGACGACAATAATTACAACTATTATGA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!	330
	AAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-B5 SEQ ID No. 39, 289, 290
1:	AlaValValLeuThrGlnThrProSerSerSerSerAlaAlaValGlyGlyThrValThr
	GCCGTCGTGCTGACCCAGACTCCATCATCCTCGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGCAGCACGACTGGGTCTGAGGTAGTAGGAGCAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnSerValTyrAsnAsnAsnTyrLeuSerTrpTyrGlnGln
	ATCAATTGCCAGGCCAGTCAGAGTGTTTATAATAACAACTACTTATCCTGGTATCAGCAA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCAGTCTCACAAATATTATTGTTGATGAATAGGACCATAGTCGTT
1:	LysProGlyGlnProProLysLeuLeuIleTyrGlyAlaSerLysLeuAlaSerGlyVal
	AAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCCAAACTGGCATCTGGGGTC
121	---------!---------!---------!---------!---------!---------!	180
	TTTGGTCCCGTCGGAGGGTTCGAGGACTAGATACCACGTAGGTTTGACCGTAGACCCCAG
1:	ProAlaArgPheSerGlySerArgSerGlyThrAspPheThrLeuThrIleAsnAspLeu
	CCAGCGCGGTTCAGCGGCAGTAGATCTGGGACAGACTTCACTCTCACCATCAACGACCTG
181	---------!---------!---------!---------!---------!---------!	240
	GGTCGCGCCAAGTCGCCGTCATCTAGACCCTGTCTGAAGTGAGAGTGGTAGTTGCTGGAC
1:	GluCysAlaAspAlaAlaThrTyrTyrCysGlnSerThrTyrGlySerAsnSerAsnGly
	GAGTGTGCCGATGCTGCCACTTACTACTGTCAAAGTACTTATGGTAGTAATAGTAATGGT
241	---------!---------!---------!---------!---------!---------!	300
	CTCACACGGCTACGACGGTGAATGATGACAGTTTCATGAATACCATCATTATCATTACCA
1:	TrpAspAsnAlaPheGlyGlyGlyThrGluValValValArg
	TGGGATAATGCTTTCGGCGGAGGGACCGAGGTGGTCGTCAGA
301	---------!---------!---------!---------!--	342
	ACCCTATTACGAAAGCCGCCTCCCTGGCTCCACCAGCAGTCT
21626B-C2 SEQ ID No. 40, 291, 292
1:	AlaGlnValLeuThrGlnThrAlaSerProValSerAlaAlaValGlyGlyThrValThr
	GCCCAAGTGCTGACCCAGACTGCATCCCCTGTGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGTTCACGACTGGGTCTGACGTAGGGGACACAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnSerSerGlnSerIleTyrGlyAsnAsnTrpLeuGlyTrpTyrGlnGln
	ATCAATTGTCAGTCCAGTCAGAGCATTTATGGTAACAACTGGTTAGGCTGGTATCAGCAG
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACAGTCAGGTCAGTCTCGTAAATACCATTGTTGACCAATCCGACCATAGTCGTC
1:	LysProGlyGlnProProLysGlnLeuIleTyrLysAlaSerThrLeuAlaSerGlyVal
	AAACCAGGGCAGCCTCCCAAGCAACTGATCTACAAGGCTTCCACTCTGGCATCTGGGGTC
121	---------!---------!---------!---------!---------!---------!	180
	TTTGGTCCCGTCGGAGGGTTCGTTGACTAGATGTTCCGAAGGTGAGACCGTAGACCCCAG
1:	SerSerArgPheLysGlySerGlySerGlyThrGlnPheThrLeuThrIleSerAspVal
	TCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACGTG
181	---------!---------!---------!---------!---------!---------!	240
	AGTAGCGCCAAGTTTCCGTCACCTAGACCCTGTGTCAAGTGAGAGTGGTAGTCGCTGCAC
1:	GlnCysAspAspAlaAlaThrTyrTyrCysLeuGlyGluPheSerCysThrSerGlyAsp
	CAGTGTGACGATGCTGCCACTTACTACTGTCTAGGCGAATTTAGTTGTACTAGTGGTGAT
241	---------!---------!---------!---------!---------!---------!	300
	GTCACACTGCTACGACGGTGAATGATGACAGATCCGCTTAAATCAACATGATCACCACTA
1:	CysTyrThrPheGlyGlyGlyThrGluValValValLys
	TGTTATACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!---------	339
	ACAATATGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-H4 SEQ ID No. 41, 293, 294
1:	AlaLeuValMetThrGlnThrProAlaSerValSerAlaAlaValGlyGlyThrValThr
	GCCCTCGTGATGACCCAGACTCCAGCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGAGCACTACTGGGTCTGAGGTCGGAGGCACAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnSerIleHisLysTyrLeuSerTrpTyrGlnGlnLysPro
	ATCAATTGCCAGGCCAGTCAGAGCATTCATAAGTACTTATCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCAGTCTCGTAAGTATTCATGAATAGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyValProSer
	GGGCAGCCTCCCAAACTCCTGATTTACAGGGCATCCACTCTGGCATCTGGGGTCCCGTCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTTGAGGACTAAATGTCCCGTAGGTGAGACCGTAGACCCCAGGGCAGC
1:	ArgPheLysGlySerGlySerGlyThrGluPheThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATTAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCACCTAGACCCTGTCTCAAGTGAGAGTGGTAATCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleAsnIleAspAsnSer
	GCCGATGCTGCCACTTACTACTGTCAACAGGATGCTGCCGTTATTAATATTGATAACAGT
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTTGTCCTACGACGGCAATAATTATAACTATTGTCA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTCGTCAAA
301	---------!---------!---------!------	336
	AAGCCGCCTCCCTGGCTCCACCAGCAGTTT
21626B-C8 SEQ ID No. 42, 295, 296
1:	AlaLeuValLeuThrGlnThrProSerSerLysSerValProValGlyAspThrValThr
	GCGCTCGTGCTGACCCAGACTCCATCTTCCAAGTCTGTCCCTGTGGGAGACACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGCGAGCACGACTGGGTCTGAGGTAGAAGGTTCAGACAGGGACACCCTCTGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGluSerValTyrAsnLysAsnTyrLeuAlaTrpPheGlnGln
	ATCAATTGCCAGGCCAGTGAGAGTGTTTATAATAAGAACTACTTAGCCTGGTTTCAGCAG
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCACTCTCACAAATATTATTCTTGATGAATCGGACCAAAGTCGTC
1:	LysProGlyGlnProProLysLeuLeuIleTyrLysAlaSerThrLeuAlaSerGlyVal
	AAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAAGGCTTCCACTCTGGCATCTGGGGTC
121	---------!---------!---------!---------!---------!---------!	180
	TTTGGTCCCGTCGGAGGGTTCGAGGACTAGATGTTCCGAAGGTGAGACCGTAGACCCCAG
1:	ProSerArgPheLysGlySerGlySerGlyThrGlnPheThrLeuThrIleAsnAspVal
	CCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAACGATGTG
181	---------!---------!---------!---------!---------!---------!	240
	GGTAGCGCCAAGTTTCCGTCACCTAGACCCTGTGTCAAGTGAGAGTGGTAGTTGCTACAC
1:	ValCysAspAspAlaAlaThrTyrPheCysAlaGlyTyrLysAspAlaAlaThrAspGly
	GTGTGTGACGATGCTGCCACTTACTTTTGTGCAGGATATAAAGATGCTGCTACTGATGGT
241	---------!---------!---------!---------!---------!---------!	300
	CACACACTGCTACGACGGTGAATGAAAACACGTCCTATATTTCTACGACGATGACTACCA
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-E6 SEQ ID No. 43, 297, 298
1:	AlaLeuValLeuThrGlnThrProSerSerLysSerValProValGlyAspThrValThr
	GCGCTGGTGCTGACCCAGACTCCATCTTCCAAGTCTGTCCCTGTGGGAGACACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGCGACCACGACTGGGTCTGAGGTAGAAGGTTCAGACAGGGACACCCTCTGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGluSerValTrpAsnLysAsnTyrLeuAlaTrpPheGlnGln
	ATCAATTGCCAGGCCAGTGAGAGTGTTTGGAATAAGAACTACTTAGCCTGGTTTCAACAG
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCACTCTCACAAACCTTATTCTTGATGAATCGGACCAAAGTTGTC
1:	LysProGlyGlnProProLysLeuLeuIleTyrLysAlaSerThrLeuAlaSerGlyVal
	AAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAAGGCTTCCACTCTGGCATCTGGGGTC
121	---------!---------!---------!---------!---------!---------!	180
	TTTGGTCCCGTCGGAGGGTTCGAGGACTAGATGTTCCGAAGGTGAGACCGTAGACCCCAG
1:	ProSerArgPheLysGlySerGlySerGlyThrGlnPheThrLeuThrIleAsnAspVal
	CCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAATTCACTCTCACCATCAACGATGTG
181	---------!---------!---------!---------!---------!---------!	240
	GGTAGCGCCAAGTTTCCGTCACCTAGACCCTGTGTTAAGTGAGAGTGGTAGTTGCTACAC
1:	ValCysGlyAspAlaAlaThrTyrPheCysAlaGlyTyrLysAspIleAspIleAspGly
	GTGTGTGGCGATGCTGCCACTTACTTTTGTGCAGGATATAAAGATATTGATATTGATGGT
241	---------!---------!---------!---------!---------!---------!	300
	CACACACCGCTACGACGGTGAATGAAAACACGTCCTATATTTCTATAACTATAACTACCA
1:	AsnAlaPheGlyGlyGlyThrGluValValValLys
	AATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TTACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT
21626B-G5 SEQ ID No. 44, 299, 300
1:	AspProValMetThrGlnThrProSerSerThrSerAlaAlaValGlyGlyThrValThr
	GACCCTGTGATGACCCAGACTCCATCTTCCACGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTGGGACACTACTGGGTCTGAGGTAGAAGGTGCAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnSerValAlaThrLysAsnGlnLeuAlaTrpTyrGlnGln
	ATCAATTGCCAGGCCAGTCAAAGTGTTGCTACTAAGAACCAATTAGCCTGGTATCAGCAG
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCAGTTTCACAACGATGATTCTTGGTTAATCGGACCATAGTCGTC
1:	LysProGlyGlnProProLysLeuLeuIleTyrThrThrSerArgLeuAlaSerGlyVal
	AAACCAGGGCAGCCTCCCAAGCTCCTGATCTATACTACATCCAGACTGGCATCTGGGGTC
121	---------!---------!---------!---------!---------!---------!	180
	TTTGGTCCCGTCGGAGGGTTCGAGGACTAGATATGATGTAGGTCTGACCGTAGACCCCAG
1:	ProSerArgPheSerGlySerGlySerGlyAlaGInPheThrLeuThrIleSerGlyVal
	CCATCGCGGTTCAGCGGCAGTGGATCTGGGGCGCAGTTCACTCTCACCATCAGTGGTGTG
181	---------!---------!---------!---------!---------!---------!	240
	GGTAGCGCCAAGTCGCCGTCACCTAGACCCCGCGTCAAGTGAGAGTGGTAGTCACCACAC
1:	GlnCysAspAspAlaAlaThrTyrTyrCysLeuGlyThrTyrAlaAsnProIleTyrThr
	CAGTGTGACGATGCTGCCACTTACTACTGTCTAGGAACATATGCTAATCCTATTTATACT
241	---------!---------!---------!---------!---------!---------!	300
	GTCACACTGCTACGACGGTGAATGATGACAGATCCTTGTATACGATTAGGATAAATATGA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACTGAGGTGGTCGTCAAG
301	---------!---------!---------!	330
	AAGCCGCCTCCCTGACTCCACCAGCAGTTC
21626B-H3 SEQ ID No. 45, 301, 302
1:	AlaLeuValMetThrGlnThrProAlaSerValSerAlaAlaValGlyGlyThrValThr
	GCCCTTGTGATGACCCAGACTCCAGCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGAACACTACTGGGTCTGAGGTCGGAGGCACAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnSerIleHisLysTyrLeuSerTrpTyrGlnGlnLysPro
	ATCAACTGCCAGGCCAGTCAGAGCATTCATAAGTACTTATCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTGACGGTCCGGTCAGTCTCGTAAGTATTCATGAATAGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyValProSer
	GGGCAGCCTCCCAAACTCCTGATTTACAGGGCATCCACTCTGGCATCTGGGGTCCCGTCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTTGAGGACTAAATGTCCCGTAGGTGAGACCGTAGACCCCAGGGCAGC
1:	ArgPheLysGlySerGlySerGlyThrGlnPheThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATTAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCACCTAGACCCTGTGTCAAGTGAGAGTGGTAATCGCTGGACCTCACA
1:	AspAspAlaAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleSerIleAspAsnSer
	GACGATGCTGCCACTTACTACTGTCAACAGGATGCTGCCGTTATTAGTATTGATAACAGT
241	---------!---------!---------!---------!---------!---------!	300
	CTGCTACGACGGTGAATGATGACAGTTGTCCTACGACGGCAATAATCATAACTATTGTCA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTCGTCAAA
301	---------!---------!---------!	330
	AAGCCGCCTCCCTGGCTCCACCAGCAGTTT
21626B-A8 SEQ ID No. 46, 303, 304
1:	AlaLeuValMetThrGlnThrProSerSerValSerAlaValValGlyGlyThrValThr
	GCGCTTGTGATGACCCAGACTCCATCCTCCGTGTCTGCAGTTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGCGAACACTACTGGGTCTGAGGTAGGAGGCACAGACGTCAACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnSerIleSerSerTyrLeuSerTrpTyrGlnGlnLysPro
	ATCAATTGCCAGGCAAGTCAGAGCATTAGTAGTTACTTGTCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGTTCAGTCTCGTAATCATCAATGAACAGGACCATAGTCGTCTTTGGT
1:	GlyGlnArgProLysProLeuIleTyrGluAlaSerLysLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCAAGCCCCTGATCTACGAAGCATCCAAACTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGTTCGGGGACTAGATGCTTCGTAGGTTTGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerGlySerGlyThrGluPheThrLeuThrIleSerGlyValGluCys
	CGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGGCGTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCACCTAGACCCTGTCTCAAGTGAGAGTGGTAGTCGCCGCACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnGlnAspAlaAlaValMetAsnValAspAsnThr
	GCCGATGCTGCCACTTACTACTGTCAACAGGATGCTGCTGTTATGAATGTTGATAATACT
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTTGTCCTACGACGACAATACTTACAACTATTATGA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTGGTCAAG
301	---------!---------!---------!	330
	AAGCCGCCTCCCTGGCTCCACCACCAGTTC
21626B-D1 SEQ ID No. 47, 305, 306
1:	AlaLeuValMetThrGlnThrProAlaSerValSerAlaAlaValGlyGlyThrValThr
	GCCCTTGTGATGACCCAGACTCCAGCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGGGAACACTACTGGGTCTGAGGTCGGAGGCACAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerArgSerIleHisLysTyrLeuSerTrpTyrGlnGlnLysPro
	ATCAATTGCCAGGCCAGTCGGAGCATTCATAAGTACTTATCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCAGCCTCGTAAGTATTCATGAATAGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyValProSer
	GGGCAGCCTCCCAAACTCCTGATTTACAGGGCATCCACTCTGGCATCTGGGGTCCCGTCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTTGAGGACTAAATGTCCCGTAGGTGAGACCGTAGACCCCAGGGCAGC
1:	ArgPheLysGlySerGlySerGlyThrGluPheThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATTAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCACCTAGACCCTGTCTCAAGTGAGAGTGGTAATCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleAsnIleAspAsnSer
	GCCGATGCTGCCACTTACTACTGTCAACAGGATGCTGCCGTTATTAATATTGATAACAGT
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTTGTCCTACGACGGCAATAATTATAACTATTGTCA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTCGTCAAA
301	---------!---------!---------!	330
	AAGCCGCCTCCCTGGCTCCACCAGCAGTTT
21626B-G1 SEQ ID No. 48, 307, 308
1:	AlaLeuValMetThrGlnThrAlaSerProValSerAlaAlaValGlyGlyThrValThr
	GCGCTGGTGATGACCCAGACTGCATCCCCCGTGTCTGCGGCTGTTGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGCGACCACTACTGGGTCTGACGTAGGGGGCACAGACGCCGACAACCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnSerIleHisLysTyrLeuSerTrpTyrGlnGlnLysPro
	ATCAATTGCCAGGCCAGTCAGAGCATTCATAAGTACTTATCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGGTCAGTCTCGTAAGTATTCATGAATAGGACCATAGTCGTCTTTGGT
1:	GlyGlnProProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyValProSer
	GGGCAGCCTCCCAAACTCCTGATTTACAGGGCATCCACTCTGGCATCTGGGGTCCCGTCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGGAGGGTTTGAGGACTAAATGTCCCGTAGGTGAGACCGTAGACCCCAGGGCAGC
1:	ArgPheLysGlySerGlySerGlyThrGluPheThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATTAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCACCTAGACCCTGTCTCAAGTGAGAGTGGTAATCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleAsnIleAspAsnSer
	GCCGATGCTGCCACTTACTACTGTCAACAGGATGCTGCCGTTATTAATATTGATAACAGT
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTTGTCCTACGACGGCAATAATTATAACTATTGTCA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTCGTCAAA
301	---------!---------!---------!	330
	AAGCCGCCTCCCTGGCTCCACCAGCAGTTT
21626B-C4-8 SEQ ID No. 49, 309, 310
1:	AlaLeuValMetThrGlnThrProSerSerValSerAlaAlaValGlyGlyThrValThr
	GCGCTTGTGATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CGCGAACACTACTGGGTCTGAGGTAGGAGGCACAGACGTCGACACCCTCCGTGTCAGTGG
1:	IleAsnCysGlnAlaSerGlnSerIleSerSerTyrLeuSerTrpTyrGlnGlnLysPro
	ATCAATTGCCAGGCAAGTCAGAGCATTAGTAGTTACTTATCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTAACGGTCCGTTCAGTCTCGTAATCATCAATGAATAGGACCATAGTCGTCTTTGGT
1:	GlyGlnArgProLysProLeuIleTyrGluThrSerLysLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCAAGCCCCTGATCTACGAAACATCCAAACTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGTTCGGGGACTAGATGCTTTGTAGGTTTGACCGTAGACCCCAGAGTAGC
1:	ArgPheSerGlySerGlySerGlyThrGluPheThrLeuThrIleSerGlyValGluCys
	CGGTTCAGTGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGGCGTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTCACCGTCACCTAGACCCTGTCTCAAGTGAGAGTGGTAGTCGCCGCACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnGlnAspAlaGlyValIleAsnValHisAsnThr
	GCCGATGCTGCCACTTACTACTGTCAACAGGATGCTGGTGTTATTAATGTTCATAATACT
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTTGTCCTACGACCACAATAATTACAAGTATTATGA
1:	PheGlyGlyGlyThrGluValValValLys
	TTCGGCGGAGGGACCGAGGTGGTGGTCAAG
301	---------!---------!---------!	330
	AAGCCGCCTCCCTGGCTCCACCACCAGTTC
21626S-A1 SEQ ID No. 50, 311, 312
1:	AspValValMetThrGlnThrProAlaSerValSerGluProValGlyGlyThrValThr
	GATGTTGTGATGACCCAGACTCCAGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACC
1	---------!---------!---------!---------!---------!---------!	60
	CTACAACACTACTGGGTCTGAGGTCGGAGGCACAGACTTGGACACCCTCCGTGTCAGTGG
1:	IleLysCysGlnAlaSerGlnSerIleGlyAsnAlaLeuAlaTrpTyrGlnGlnLysPro
	ATCAAGTGCCAGGCCAGTCAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGAAACCA
61	---------!---------!---------!---------!---------!---------!	120
	TAGTTCACGGTCCGGTCAGTCTCGTAACCGTTACGTAATCGGACCATAGTCGTCTTTGGT
1:	GlyGlnArgProSerLeuLeuIleTyrAspAlaSerThrLeuAlaSerGlyValSerSer
	GGGCAGCGTCCCTCGCTCCTGATCTATGATGCATCCACTCTGGCATCTGGGGTCTCATCG
121	---------!---------!---------!---------!---------!---------!	180
	CCCGTCGCAGGGAGCGAGGACTAGATACTACGTAGGTGAGACCGTAGACCCCAGAGTAGC
1:	ArgPheLysGlySerArgSerGlyThrGluTyrThrLeuThrIleSerAspLeuGluCys
	CGGTTCAAAGGCAGTAGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGT
181	---------!---------!---------!---------!---------!---------!	240
	GCCAAGTTTCCGTCATCTAGACCCTGTCTCATGTGAGAGTGGTAGTCGCTGGACCTCACA
1:	AlaAspAlaAlaThrTyrTyrCysGlnCysAlaTyrTyrGlySerArgTyrAlaGlyGly
	GCCGATGCTGCCACTTACTACTGTCAGTGTGCTTACTATGGTAGCCGTTATGCTGGAGGG
241	---------!---------!---------!---------!---------!---------!	300
	CGGCTACGACGGTGAATGATGACAGTCACACGAATGATACCATCGGCAATACGACCTCCC
1:	SerAlaPheGlyGlyGlyThrGluValValValLys
	AGTGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAA
301	---------!---------!---------!------	336
	TCACGAAAGCCGCCTCCCTGGCTCCACCACCAGTTT

CDR Sequences

Listed below are sequences listing of certain non-limiting anti-IgE antibodies, identified by name (e.g. “21626S-D5 . . . ”) and, where appropriate, ID number (e.g. “SEQ ID No. 51 . . . ”).

HCDR1

HCDR2

HCDR3

LCDR1

LCDR2

LCDR3

Clone

Sequence

SEQ ID No.

Sequence

SEQ ID No.

Sequence

SEQ ID No.

Sequence

SEQ ID No.

Sequence

SEQ ID No.

Sequence

SEQ ID No.

indicates data missing or illegible when filed

Humanized Heavy Chain Sequences (Variable Region)

Listed below are humanized heavy chain sequences (variable region) of certain non-limiting anti-IgE antibodies, identified by name (e.g. “h-21626B-C4-8”) and ID number (e.g. “SEQ ID No. 201”).

h-21626B-C4-8 SEQ ID No. 201, 313, 314
1:	1	LeuGluGluValGlnLeuValGluSerGlyGlyGlyLeuValGlnProGlyGlySerLeu	60
		CTCGAGGAGGTCCAGCTCGTTGAGTCTGGAGGAGGCTTGGTCCAGCCTGGAGGGTCCCTG
		---------!---------!---------!---------!---------!---------!
		GAGCTCCTCCAGGTCGAGCAACTCAGACCTCCTCCGAACCAGGTCGGACCTCCCAGGGAC
1:	61	ArgLeuSerCysThrAlaSerGlyPheSerLeuSerSerTyrTyrMetSerTrpValArg	120
		AGGCTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGCTACTACATGAGCTGGGTAAGA
		---------!---------!---------!---------!---------!---------!
		TCCGAGAGGACATGTCGGAGACCTAAGAGGGAGTCATCGATGATGTACTCGACCCATTCT
1:	121	GlnAlaProGlyLysGlyLeuGluTrpIleGlyIleIleTyrProSerGlyAsnThrTyr	180
		CAGGCACCAGGGAAGGGACTGGAGTGGATCGGCATCATTTATCCTAGTGGTAACACATAC
		---------!---------!---------!---------!---------!---------!
		GTCCGTGGTCCCTTCCCTGACCTCACCTAGCCGTAGTAAATAGGATCACCATTGTGTATG
1:	181	TyrAlaAsnTrpAlaAsnGlyArgPheThrIleSerArgHisAsnSerLysAsnThrLeu	240
		TACGCGAACTGGGCAAATGGTCGATTCACCATCTCCAGACACAATTCCAAGAACACGCTG
		---------!---------!---------!---------!---------!---------!
		ATGCGCTTGACCCGTTTACCAGCTAAGTGGTAGAGGTCTGTGTTAAGGTTCTTGTGCGAC
1:	241	TyrLeuGlnMetAsnSerLeuArgAlaGluAspThrAlaValTyrTyrCysAlaArgAsp	300
		TATCTTCAAATGAACAGCCTGAGAGCGGAGGACACGGCCGTGTACTACTGTGCCAGAGAT
		---------!---------!---------!---------!---------!---------!
		ATAGAAGTTTACTTGTCGGACTCTCGCCTCCTGTGCCGGCACATGATGACACGGTCTCTA
1:	301	SerGlyTyrProAspIleTrpGlyGlnGlyThrLeuValThrValSerSer	351
		TCTGGTTATCCTGACATCTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCA
		---------!---------!---------!---------!---------!-
		AGACCAATAGGACTGTAGACCCCAGTTCCTTGGGACCAGTGGCAGAGGAGT
h-21626B-H3 SEQ ID No. 202, 315, 316
1:	1	LeuGluGlnValGlnLeuValGluSerGlyGlyGlyLeuValGlnProGlyGlySerLeu	60
		CTCGAGCAGGTCCAGCTGGTTGAGTCTGGGGGAGGCTTGGTCCAGCCTGGAGGGTCCCTG
		---------!---------!---------!---------!---------!---------!
		GAGCTCGTCCAGGTCGACCAACTCAGACCCCCTCCGAACCAGGTCGGACCTCCCAGGGAC
1:	61	ArgLeuSerCysThrAlaSerGlyPheSerLeuSerSerTyrAlaMetGlyTrpValArg	120
		AGGCTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGCTATGCAATGGGCTGGGTAAGA
		---------!---------!---------!---------!---------!---------!
		TCCGAGAGGACATGTCGGAGACCTAAGAGGGAGTCATCGATACGTTACCCGACCCATTCT
1:	121	GlnAlaProGlyLysGlyLeuGluTyrIleGlyTrpIleSerAlaGlyGlyThrThrTyr	180
		CAGGCACCAGGGAAGGGACTTGAGTACATCGGCTGGATTAGTGCTGGTGGTACCACATAC
		---------!---------!---------!---------!---------!---------!
		GTCCGTGGTCCCTTCCCTGAACTCATGTAGCCGACCTAATCACGACCACCATGGTGTATG
1:	181	TyrAlaSerTrpValAsnSerArgPheThrIleSerArgAspAsnSerLysAsnThrLeu	240
		TACGCGAGCTGGGTGAATAGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
		---------!---------!---------!---------!---------!---------!
		ATGCGCTCGACCCACTTATCGTCTAAGTGGTAGAGGTCTCTGTTAAGGTTCTTGTGCGAC
1:	241	TyrLeuGlnMetAsnSerLeuArgAlaGluAspThrAlaValTyrTyrCysAlaArgGlu	300
		TATCTTCAAATGAACAGCCTGAGAGCGGAGGACACGGCCGTGTACTACTGTGCCAGAGAG
		---------!---------!---------!---------!---------!---------!
		ATAGAAGTTTACTTGTCGGACTCTCGCCTCCTGTGCCGGCACATGATGACACGGTCTCTC
1:	301	GlyThrGlyTrpGlyAlaTyrAspIleTrpGlyGlnGlyThrLeuValThrValSerSer	360
		GGTACTGGCTGGGGTGCCTATGACATCTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCA
		---------!---------!---------!---------!---------!---------!
		CCATGACCGACCCCACGGATACTGTAGACCCCAGTTCCTTGGGACCAGTGGCAGAGGAGT

Humanized Light Chain Sequences (Variable Region)

Listed below are humanized light chain sequences (variable region) of certain non-limiting anti-IgE antibodies, identified by name (e.g. “h-21626B-C4-8”) and ID number (e.g. “SEQ ID No. 203”).

h-21626B-C4-8 SEQ ID No. 203, 315, 316
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	61	ValThrIleThrCysGlnAlaSerGlnSerIleSerSerTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCAAGTCAGAGCATTAGTAGTTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGTTCAGTCTCGTAATCATCAATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrGluThrSerLysLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATGAAACATCCAAACTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATACTTTGTAGGTTTGACCGTAGACCCCAG
1:	181	ProSerArgPheSerGlySerGlySerGlyThrAspPheThrLeuThrIleSerSerLeu	240
		CCCTCAAGGTTTAGTGGAAGTGGATCTGGGACAGATTTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATCACCTTCACCTAGACCCTGTCTAAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaGlyValIleAsnValHis	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGGTGTTATTAATGTTCAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACCACAATAATTACAAGTA
1:	301	AsnThrPheGlyGlyGlyThrLysValGluIleLys	336
		AATACTTTCGGTGGTGGTACAAAGGTCGAGATCAAA
		---------!---------!---------!------
		TTATGAAAGCCACCACCATGTTTCCAGCTCTAGTTT
h-21626B-C4-8E SEQ ID No. 204, 315, 316
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	61	ValThrIleThrCysGlnAlaSerGlnSerIleSerSerTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCAAGTCAGAGCATTAGTAGTTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGTTCAGTCTCGTAATCATCAATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrGluThrSerLysLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATGAAACATCCAAACTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATACTTTGTAGGTTTGACCGTAGACCCCAG
1:	181	ProSerArgPheSerGlySerGlySerGlyThrGluPheThrLeuThrIleSerSerLeu	240
		CCCTCAAGGTTTAGTGGAAGTGGATCTGGGACAGAATTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATCACCTTCACCTAGACCCTGTCTTAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaGlyValIleAsnValHis	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGGTGTTATTAATGTTCAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACCACAATAATTACAAGTA
1:	301	AsnThrPheGlyGlyGlyThrLysValGluIleLys	336
		AATACTTTCGGTGGTGGTACAAAGGTCGAGATCAAA
		---------!---------!---------!------
		TTATGAAAGCCACCACCATGTTTCCAGCTCTAGTTT
h-21626B-H3 SEQ ID No. 205, 321, 322
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	61	ValThrIleThrCysGlnAlaSerGlnSerIleHisLysTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCCAGTCAGAGCATTCATAAGTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGGTCAGTCTCGTAAGTATTCATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATAGGGCATCCACTCTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATATCCCGTAGGTGAGACCGTAGACCCCAG
1:	181	ProSerArgPheSerGlySerGlySerGlyThrAspPheThrLeuThr IleSerSerLeu	240
		CCCTCAAGGTTTAGTGGAAGTGGATCTGGGACAGATTTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATCACCTTCACCTAGACCCTGTCTAAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleSerIleAsp	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGCCGTTATTAGTATTGAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACGGCAATAATCATAACTA
1:	301	AsnSerPheGlyGlyGlyThrLysValGluIleLys	336
		AACAGTTTCGGTGGTGGTACAAAGGTCGAGATCAAA
		---------!---------!---------!------
		TTGTCAAAGCCACCACCATGTTTCCAGCTCTAGTTT
h-21626B-H3KQ SEQ ID No. 206, 323, 324
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	60	ValThrIleThrCysGlnAlaSerGlnSerIleHisLysTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCCAGTCAGAGCATTCATAAGTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGGTCAGTCTCGTAAGTATTCATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATAGGGCATCCACTCTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATATCCCGTAGGTGAGACCGTAGACCCCAG
1:	181	ProSerArgPheLysGlySerGlySerGlyThrGlnPheThrLeuThrIleSerSerLeu	240
		CCCTCAAGGTTTAAGGGAAGTGGATCTGGGACACAGTTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATTCCCTTCACCTAGACCCTGTGTCAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleSerIleAsp	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGCCGTTATTAGTATTGAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACGGCAATAATCATAACTA
1:	301	AsnSerPheGlyGlyGlyThrLysValGluIleLys	336
		AACAGTTTCGGTGGTGGTACAAAGGTCGAGATCAAA
		---------!---------!---------!------
		TTGTCAAAGCCACCACCATGTTTCCAGCTCTAGTTT

Humanized Heavy Chain Sequences (Full Sequence)

Listed below are humanized heavy chain sequences (full sequence) of certain non-limiting anti-IgE antibodies, identified by name (e.g. “h-21626B-C4-8”) and ID number (e.g. “SEQ ID No. 207”).

h-21626B-C4-8 SEQ ID No. 207, 325, 326
1:	1	LeuGluGluValGlnLeuValGluSerGlyGlyGlyLeuValGlnProGlyGlySerLeu	60
		CTCGAGGAGGTCCAGCTCGTTGAGTCTGGAGGAGGCTTGGTCCAGCCTGGAGGGTCCCTG
		---------!---------!---------!---------!---------!---------!
		GAGCTCCTCCAGGTCGAGCAACTCAGACCTCCTCCGAACCAGGTCGGACCTCCCAGGGAC
1:	60	ArgLeuSerCysThrAlaSerGlyPheSerLeuSerSerTyrTyrMetSerTrpValArg	120
		AGGCTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGCTACTACATGAGCTGGGTAAGA
		---------!---------!---------!---------!---------!---------!
		TCCGAGAGGACATGTCGGAGACCTAAGAGGGAGTCATCGATGATGTACTCGACCCATTCT
1:	121	GlnAlaProGlyLysGlyLeuGluTrpIleGlyIleIleTyrProSerGlyAsnThrTyr	180
		CAGGCACCAGGGAAGGGACTGGAGTGGATCGGCATCATTTATCCTAGTGGTAACACATAC
		---------!---------!---------!---------!---------!---------!
		GTCCGTGGTCCCTTCCCTGACCTCACCTAGCCGTAGTAAATAGGATCACCATTGTGTATG
1:	181	TyrAlaAsnTrpAlaAsnGlyArgPheThrIleSerArgHisAsnSerLysAsnThrLeu	240
		TACGCGAACTGGGCAAATGGTCGATTCACCATCTCCAGACACAATTCCAAGAACACGCTG
		---------!---------!---------!---------!---------!---------!
		ATGCGCTTGACCCGTTTACCAGCTAAGTGGTAGAGGTCTGTGTTAAGGTTCTTGTGCGAC
1:	241	TyrLeuGlnMetAsnSerLeuArgAlaGluAspThrAlaValTyrTyrCysAlaArgAsp	300
		TATCTTCAAATGAACAGCCTGAGAGCGGAGGACACGGCCGTGTACTACTGTGCCAGAGAT
		---------!---------!---------!---------!---------!---------!
		ATAGAAGTTTACTTGTCGGACTCTCGCCTCCTGTGCCGGCACATGATGACACGGTCTCTA
1:	301	SerGlyTyrProAspIleTrpGlyGlnGlyThrLeuValThrValSerSerAlaSerThr	360
		TCTGGTTATCCTGACATCTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCAGCCTCCACC
		---------!---------!---------!---------!---------!---------!
		AGACCAATAGGACTGTAGACCCCAGTTCCTTGGGACCAGTGGCAGAGGAGTCGGAGGTGG
1:	361	LysGlyProSerValPheProLeuAlaProSerSerLysSerThrSerGlyGlyThrAla	420
		AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG
		---------!---------!---------!---------!---------!---------!
		TTCCCGGGTAGCCAGAAGGGGGACCGTGGGAGGAGGTTCTCGTGGAGACCCCCGTGTCGC
1:	421	AlaLeuGlyCysLeuValLysAspTyrPheProGluProValThrValSerTrpAsnSer	480
		GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCA
		---------!---------!---------!---------!---------!---------!
		CGGGACCCGACGGACCAGTTCCTGATGAAGGGGCTTGGCCACTGCCACAGCACCTTGAGT
1:	481	GlyAlaLeuThrSerGlyValHisThrPheProAlaValLeuGlnSerSerGlyLeuTyr	540
		GGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTAC
		---------!---------!---------!---------!---------!---------!
		CCGCGGGACTGGTCGCCGCACGTGTGGAAGGGCCGACAGGATGTCAGGAGTCCTGAGATG
1:	541	SerLeuSerSerValValThrValProSerSerSerLeuGlyThrGlnThrTyrIleCys	600
		TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGC
		---------!---------!---------!---------!---------!---------!
		AGGGAGTCGTCGCACCACTGGCACGGGAGGTCGTCGAACCCGTGGGTCTGGATGTAGACG
1:	601	AsnValAsnHisLysProSerAsnThrLysValAspLysLysValGluProLysSerCys	660
		AACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGT
		---------!---------!---------!---------!---------!---------!
		TTGCACTTAGTGTTCGGGTCGTTGTGGTTCCACCTGTTCTTTCAACTCGGGTTTAGAACA
1:	661	AspLys	666
		GACAAA
		------
		CTGTTT
h-21626B-H3 SEQ ID No. 208, 327, 328
1:	1	LeuGluGlnValGlnLeuValGluSerGlyGlyGlyLeuValGlnProGlyGlySerLeu	60
		CTCGAGCAGGTCCAGCTGGTTGAGTCTGGGGGAGGCTTGGTCCAGCCTGGAGGGTCCCTG
		---------!---------!---------!---------!---------!---------!
		GAGCTCGTCCAGGTCGACCAACTCAGACCCCCTCCGAACCAGGTCGGACCTCCCAGGGAC
1:	61	ArgLeuSerCysThrAlaSerGlyPheSerLeuSerSerTyrAlaMetGlyTrpValArg	120
		AGGCTCTCCTGTACAGCCTCTGGATTCTCCCTCAGTAGCTATGCAATGGGCTGGGTAAGA
		---------!---------!---------!---------!---------!---------!
		TCCGAGAGGACATGTCGGAGACCTAAGAGGGAGTCATCGATACGTTACCCGACCCATTCT
1:	121	GlnAlaProGlyLysGlyLeuGluTyrIleGlyTrpIleSerAlaGlyGlyThrThrTyr	180
		CAGGCACCAGGGAAGGGACTTGAGTACATCGGCTGGATTAGTGCTGGTGGTACCACATAC
		---------!---------!---------!---------!---------!---------!
		GTCCGTGGTCCCTTCCCTGAACTCATGTAGCCGACCTAATCACGACCACCATGGTGTATG
1:	181	TyrAlaSerTrpValAsnSerArgPheThrIleSerArgAspAsnSerLysAsnThrLeu	240
		TACGCGAGCTGGGTGAATAGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG
		---------!---------!---------!---------!---------!---------!
		ATGCGCTCGACCCACTTATCGTCTAAGTGGTAGAGGTCTCTGTTAAGGTTCTTGTGCGAC
1:	241	TyrLeuGlnMetAsnSerLeuArgAlaGluAspThrAlaValTyrTyrCysAlaArgGlu	300
		TATCTTCAAATGAACAGCCTGAGAGCGGAGGACACGGCCGTGTACTACTGTGCCAGAGAG
		---------!---------!---------!---------!---------!---------!
		ATAGAAGTTTACTTGTCGGACTCTCGCCTCCTGTGCCGGCACATGATGACACGGTCTCTC
1:	301	GlyThrGlyTrpGlyAlaTyrAspIleTrpGlyGlnGlyThrLeuValThrValSerSer	360
		GGTACTGGCTGGGGTGCCTATGACATCTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCA
		---------!---------!---------!---------!---------!---------!
		CCATGACCGACCCCACGGATACTGTAGACCCCAGTTCCTTGGGACCAGTGGCAGAGGAGT
1:	361	AlaSerThrLysGlyProSerValPheProLeuAlaProSerSerLysSerThrSerGly	420
		GCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGG
		---------!---------!---------!---------!---------!---------!
		CGGAGGTGGTTCCCGGGTAGCCAGAAGGGGGACCGTGGGAGGAGGTTCTCGTGGAGACCC
1:	421	GlyThrAlaAlaLeuGlyCysLeuValLysAspTyrPheProGluProValThrValSer	480
		GGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCG
		---------!---------!---------!---------!---------!---------!
		CCGTGTCGCCGGGACCCGACGGACCAGTTCCTGATGAAGGGGCTTGGCCACTGCCACAGC
1:	481	TrpAsnSerGlyAlaLeuThrSerGlyValHisThrPheProAlaValLeuGlnSerSer	540
		TGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
		---------!---------!---------!---------!---------!---------!
		ACCTTGAGTCCGCGGGACTGGTCGCCGCACGTGTGGAAGGGCCGACAGGATGTCAGGAGT
1:	541	GlyLeuTyrSerLeuSerSerValValThrValProSerSerSerLeuGlyThrGlnThr	600
		GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACC
		---------!---------!---------!---------!---------!---------!
		CCTGAGATGAGGGAGTCGTCGCACCACTGGCACGGGAGGTCGTCGAACCCGTGGGTCTGG
1:	601	TyrIleCysAsnValAsnHisLysProSerAsnThrLysValAspLysLysValGluPro	660
		TACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCC
		---------!---------!---------!---------!---------!---------!
		ATGTAGACGTTGCACTTAGTGTTCGGGTCGTTGTGGTTCCACCTGTTCTTTCAACTCGGG
1:	661	LysSerCysAspLys	675
		AAATCTTGTGACAAA
		---------!-----
		TTTAGAACACTGTTT

Humanized Light Chain Sequences (Full Sequence)

Listed below are humanized light chain sequences (full sequence) of certain non-limiting anti-IgE antibodies, identified by name (e.g. “h-21626B-C4-8”) and ID number (e.g. “SEQ ID No. 209”).

h-21626B-C4-8 SEQ ID No. 209, 329, 330
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	61	ValThrIleThrCysGlnAlaSerGlnSerIleSerSerTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCAAGTCAGAGCATTAGTAGTTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGTTCAGTCTCGTAATCATCAATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrGluThrSerLysLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATGAAACATCCAAACTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATACTTTGTAGGTTTGACCGTAGACCCCAG
1:	181	ProSerArgPheSerGlySerGlySerGlyThrAspPheThrLeuThrIleSerSerLeu	240
		CCCTCAAGGTTTAGTGGAAGTGGATCTGGGACAGATTTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATCACCTTCACCTAGACCCTGTCTAAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaGlyValIleAsnValHis	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGGTGTTATTAATGTTCAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACCACAATAATTACAAGTA
1:	301	AsnThrPheGlyGlyGlyThrLysValGluIleLysArgThrValAlaAlaProSerVal	360
		AATACTTTCGGTGGTGGTACAAAGGTCGAGATCAAACGGACTGTGGCTGCACCATCTGTC
		---------!---------!---------!---------!---------!---------!
		TTATGAAAGCCACCACCATGTTTCCAGCTCTAGTTTGCCTGACACCGACGTGGTAGACAG
1:	361	PheIlePheProProSerAspGluGlnLeuLysSerGlyThrAlaSerValValCysLeu	420
		TTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
		---------!---------!---------!---------!---------!---------!
		AAGTAGAAGGGCGGTAGACTACTCGTCAACTTTAGACCTTGACGGAGACAACACACGGAC
1:	421	LeuAsnAsnPheTyrProArgGluAlaLysValGlnTrpLysValAspAsnAlaLeuGln	480
		CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA
		---------!---------!---------!---------!---------!---------!
		GACTTATTGAAGATAGGGTCTCTCCGGTTTCATGTCACCTTCCACCTATTGCGGGAGGTT
1:	481	SerGlyAsnSerGlnGluSerValThrGluGInAspSerLysAspSerThrTyrSerLeu	540
		TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
		---------!---------!---------!---------!---------!---------!
		AGCCCATTGAGGGTCCTCTCACAGTGTCTCGTCCTGTCGTTCCTGTCGTGGATGTCGGAG
1:	541	SerSerThrLeuThrLeuSerLysAlaAspTyrGluLysHisLysValTyrAlaCysGlu	600
		AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA
		---------!---------!---------!---------!---------!---------!
		TCGTCGTGGGACTGCGACTCGTTTCGTCTGATGCTCTTTGTGTTTCAGATGCGGACGCTT
1:	601	ValThrHisGlnGlyLeuSerSerProValThrLysSerPheAsnArgGlyGluCys	657
		GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
		---------!---------!---------!---------!---------!-------
		CAGTGGGTAGTCCCGGACTCGAGCGGGCAGTGTTTCTCGAAGTTGTCCCCTCTCACA
h-21626C-C4-8E SEQ ID No. 210, 331, 332
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	61	ValThrIleThrCysGlnAlaSerGlnSerIleSerSerTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCAAGTCAGAGCATTAGTAGTTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGTTCAGTCTCGTAATCATCAATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrGluThrSerLysLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATGAAACATCCAAACTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATACTTTGTAGGTTTGACCGTAGACCCCAG
1:	181	ProSerArgPheSerGlySerGlySerGlyThrGluPheThrLeuThrIleSerSerLeu	240
		CCCTCAAGGTTTAGTGGAAGTGGATCTGGGACAGAATTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATCACCTTCACCTAGACCCTGTCTTAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaGlyValIleAsnValHis	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGGTGTTATTAATGTTCAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACCACAATAATTACAAGTA
1:	301	AsnThrPheGlyGlyGlyThrLysValGluIleLysArgThrValAlaAlaProSerVal	360
		AATACTTTCGGTGGTGGTACAAAGGTCGAGATCAAACGGACTGTGGCTGCACCATCTGTC
		---------!---------!---------!---------!---------!---------!
		TTATGAAAGCCACCACCATGTTTCCAGCTCTAGTTTGCCTGACACCGACGTGGTAGACAG
1:	361	PheIlePheProProSerAspGluGlnLeuLysSerGlyThrAlaSerValValCysLeu	420
		TTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
		---------!---------!---------!---------!---------!---------!
		AAGTAGAAGGGCGGTAGACTACTCGTCAACTTTAGACCTTGACGGAGACAACACACGGAC
1:	421	LeuAsnAsnPheTyrProArgGluAlaLysValGlnTrpLysValAspAsnAlaLeuGln	480
		CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA
		---------!---------!---------!---------!---------!---------!
		GACTTATTGAAGATAGGGTCTCTCCGGTTTCATGTCACCTTCCACCTATTGCGGGAGGTT
1:	481	SerGlyAsnSerGlnGluSerValThrGluGlnAspSerLysAspSerThrTyrSerLeu	540
		TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
		---------!---------!---------!---------!---------!---------!
		AGCCCATTGAGGGTCCTCTCACAGTGTCTCGTCCTGTCGTTCCTGTCGTGGATGTCGGAG
1:	541	SerSerThrLeuThrLeuSerLysAlaAspTyrGluLysHisLysValTyrAlaCysGlu	600
		AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA
		---------!---------!---------!---------!---------!---------!
		TCGTCGTGGGACTGCGACTCGTTTCGTCTGATGCTCTTTGTGTTTCAGATGCGGACGCTT
1:	601	ValThrHisGlnGlyLeuSerSerProValThrLysSerPheAsnArgGlyGluCys	657
		GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
		---------!---------!---------!---------!---------!-------
		CAGTGGGTAGTCCCGGACTCGAGCGGGCAGTGTTTCTCGAAGTTGTCCCCTCTCACA
h-21626B-H3 SEQ ID No. 211, 333, 334
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	61	ValThrIleThrCysGlnAlaSerGlnSerIleHisLysTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCCAGTCAGAGCATTCATAAGTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGGTCAGTCTCGTAAGTATTCATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATAGGGCATCCACTCTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATATCCCGTAGGTGAGACCGTAGACCCCAG
1:	181	ProSerArgPheSerGlySerGlySerGlyThrAspPheThrLeuThrIleSerSerLeu	240
		CCCTCAAGGTTTAGTGGAAGTGGATCTGGGACAGATTTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATCACCTTCACCTAGACCCTGTCTAAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleSerIleAsp	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGCCGTTATTAGTATTGAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACGGCAATAATCATAACTA
1:	301	AsnSerPheGlyGlyGlyThrLysValGluIleLysArgThrValAlaAlaProSerVal	360
		AACAGTTTCGGTGGTGGTACAAAGGTCGAGATCAAACGGACTGTGGCTGCACCATCTGTC
		---------!---------!---------!---------!---------!---------!
		TTGTCAAAGCCACCACCATGTTTCCAGCTCTAGTTTGCCTGACACCGACGTGGTAGACAG
1:	361	PheIlePheProProSerAspGluGlnLeuLysSerGlyThrAlaSerValValCysLeu	420
		TTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
		---------!---------!---------!---------!---------!---------!
		AAGTAGAAGGGCGGTAGACTACTCGTCAACTTTAGACCTTGACGGAGACAACACACGGAC
1:	421	LeuAsnAsnPheTyrProArgGluAlaLysValGlnTrpLysValAspAsnAlaLeuGln	480
		CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA
		---------!---------!---------!---------!---------!---------!
		GACTTATTGAAGATAGGGTCTCTCCGGTTTCATGTCACCTTCCACCTATTGCGGGAGGTT
1:	481	SerGlyAsnSerGlnGluSerValThrGluGInAspSerLysAspSerThrTyrSerLeu	540
		TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
		---------!---------!---------!---------!---------!---------!
		AGCCCATTGAGGGTCCTCTCACAGTGTCTCGTCCTGTCGTTCCTGTCGTGGATGTCGGAG
1:	541	SerSerThrLeuThrLeuSerLysAlaAspTyrGluLysHisLysValTyrAlaCysGlu	600
		AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA
		---------!---------!---------!---------!---------!---------!
		TCGTCGTGGGACTGCGACTCGTTTCGTCTGATGCTCTTTGTGTTTCAGATGCGGACGCTT
1:	601	ValThrHisGlnGlyLeuSerSerProValThrLysSerPheAsnArgGlyGluCys	657
		GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
		---------!---------!---------!---------!---------!-------
		CAGTGGGTAGTCCCGGACTCGAGCGGGCAGTGTTTCTCGAAGTTGTCCCCTCTCACA
h-21626B-H3KQ SEQ ID No. 212, 335, 336
1:	1	SerArgAspIleGlnMetThrGlnSerProSerSerLeuSerAlaSerValGlyAspArg	60
		TCTAGAGACATCCAGATGACGCAGTCCCCATCCTCCCTGTCTGCATCTGTAGGAGACAGG
		---------!---------!---------!---------!---------!---------!
		AGATCTCTGTAGGTCTACTGCGTCAGGGGTAGGAGGGACAGACGTAGACATCCTCTGTCC
1:	61	ValThrIleThrCysGlnAlaSerGlnSerIleHisLysTyrLeuSerTrpTyrGlnGln	120
		GTCACCATCACTTGCCAGGCCAGTCAGAGCATTCATAAGTACTTATCCTGGTATCAGCAG
		---------!---------!---------!---------!---------!---------!
		CAGTGGTAGTGAACGGTCCGGTCAGTCTCGTAAGTATTCATGAATAGGACCATAGTCGTC
1:	121	LysProGlyLysAlaProLysLeuLeuIleTyrArgAlaSerThrLeuAlaSerGlyVal	180
		AAGCCAGGCAAGGCACCTAAGCTCCTGATCTATAGGGCATCCACTCTGGCATCTGGGGTC
		---------!---------!---------!---------!---------!---------!
		TTCGGTCCGTTCCGTGGATTCGAGGACTAGATATCCCGTAGGTGAGACCGTAGACCCCAG
1:	181	ProSerArgPheLysGlySerGlySerGlyThrGlnPheThrLeuThrIleSerSerLeu	240
		CCCTCAAGGTTTAAGGGAAGTGGATCTGGGACACAGTTCACCCTCACCATCAGCAGTCTG
		---------!---------!---------!---------!---------!---------!
		GGGAGTTCCAAATTCCCTTCACCTAGACCCTGTGTCAAGTGGGAGTGGTAGTCGTCAGAC
1:	241	GlnProGluAspPheAlaThrTyrTyrCysGlnGlnAspAlaAlaValIleSerIleAsp	300
		CAACCGGAGGACTTCGCGACGTACTACTGCCAACAGGATGCTGCCGTTATTAGTATTGAT
		---------!---------!---------!---------!---------!---------!
		GTTGGCCTCCTGAAGCGCTGCATGATGACGGTTGTCCTACGACGGCAATAATCATAACTA
1:	301	AsnSerPheGlyGlyGlyThrLysValGluIleLysArgThrValAlaAlaProSerVal	360
		AACAGTTTCGGTGGTGGTACAAAGGTCGAGATCAAACGGACTGTGGCTGCACCATCTGTC
		---------!---------!---------!---------!---------!---------!
		TTGTCAAAGCCACCACCATGTTTCCAGCTCTAGTTTGCCTGACACCGACGTGGTAGACAG
1:	361	PheIlePheProProSerAspGluGlnLeuLysSerGlyThrAlaSerValValCysLeu	420
		TTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG
		---------!---------!---------!---------!---------!---------!
		AAGTAGAAGGGCGGTAGACTACTCGTCAACTTTAGACCTTGACGGAGACAACACACGGAC
1:	421	LeuAsnAsnPheTyrProArgGluAlaLysValGlnTrpLysValAspAsnAlaLeuGln	480
		CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA
		---------!---------!---------!---------!---------!---------!
		GACTTATTGAAGATAGGGTCTCTCCGGTTTCATGTCACCTTCCACCTATTGCGGGAGGTT
1:	481	SerGlyAsnSerGlnGluSerValThrGluGlnAspSerLysAspSerThrTyrSerLeu	540
		TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC
		---------!---------!---------!---------!---------!---------!
		AGCCCATTGAGGGTCCTCTCACAGTGTCTCGTCCTGTCGTTCCTGTCGTGGATGTCGGAG
1:	541	SerSerThrLeuThrLeuSerLysAlaAspTyrGluLysHisLysValTyrAlaCysGlu	600
		AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA
		---------!---------!---------!---------!---------!---------!
		TCGTCGTGGGACTGCGACTCGTTTCGTCTGATGCTCTTTGTGTTTCAGATGCGGACGCTT
1:	601	ValThrHisGlnGlyLeuSerSerProValThrLysSerPheAsnArgGlyGluCys	657
		GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
		---------!---------!---------!---------!---------!-------
		CAGTGGGTAGTCCCGGACTCGAGCGGGCAGTGTTTCTCGAAGTTGTCCCCTCTCACA

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

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Claims

1. An antibody or a fragment thereof, comprising a Fab region that specifically binds to an IgE, wherein the binding of the Fab to the IgE disrupts interaction between the IgE and at least one Fcε receptor.

2. The antibody or fragment of claim 1, wherein the disrupted interaction comprises blocking an unbound IgE from binding to the at least one Fcε receptor.

3. The antibody or fragment of claim 1, wherein the disrupted interaction comprises dissociating a bound IgE from the at least one Fcε receptor.

4. The antibody or fragment of claim 1, wherein the disrupted interaction results in suppression of degranulation.

5. The antibody or fragment of claim 1, wherein the at least one Fcε receptor comprises FcεRI.

6. The antigen binding polypeptide of claim 1, wherein the at least one Fcε receptor comprises CD23.

7. The antibody or fragment of claim 1, wherein the at least one Fcε receptor comprises FcεRI and CD23.

8. The antibody or fragment of claim 1, wherein the Fab region specifically binds to at least one amino acid residue in β5-helix region of the Cε2, wherein the β5-helix region is the combination of helix, β5-helix joint, and lower half of β5 that connects to helix of Cε2.

9. The antibody or fragment of claim 8, wherein the Fab region specifically binds to at least one amino acid residue in the helix of Cε2.

10. The antibody or fragment of claim 8, wherein the Fab region specifically binds to at least one amino acid residue in the β5-helix joint of Cε2.

11. The antibody or fragment of claim 8, wherein the Fab region specifically binds to at least one amino acid residue in the lower half of β5 that connects to helix of Cε2.

12. The antibody or fragment of claim 8, wherein the Fab region does not bind to amino acid residue T298 of Cε2.

13. The antibody or fragment of claim 8, wherein the Fab region binds to at least two amino acid residues in the β5-Cε2 helix region.

14. The antibody or fragment of claim 8, wherein the Fab region does not bind to β3 region of Cε2.

15. The antibody or fragment of claim 8, wherein the Fab region does not bind to β4 region of Cε2.

16. The antibody or fragment of claim 8, wherein the Fab region does not bind to β3 or β4 region of Cε2.

17. The antibody or fragment of claim 1, wherein the antibody is a bispecific antibody or a binding fragment thereof.

18. The antibody or fragment of claim 1, wherein the antibody comprises a monovalent Fab′, a divalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or binding fragment thereof.

19. The antibody or fragment of claim 1, wherein the Fab region comprises at least one heavy chain sequence selected from SEQ ID Nos 1-25.

20. The antibody or fragment of claim 1, wherein the Fab region comprises at least one light chain sequence selected from SEQ ID Nos 26-50.

21. The antibody or fragment of claim 1, wherein the Fab region comprises at least one complementarity determining region (CDR) selected from SEQ ID Nos 51-200.

22. The antibody or fragment of claim 1, wherein the antibody exhibits a KD of less than 1 nM, 1.2 nM, 2 nM, 5 nM, 10 nM, 13.5 nM, 15 nM, 20 nM, 25 nM, or 30 nM.

23. The antibody or fragment of claim 1, wherein the antibody is a humanized antibody.

24. The antibody or a fragment thereof of claim 23, wherein the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201-202.

25. The antibody or a fragment thereof of claim 23, wherein the humanized antibody comprises a light chain variable region selected from SEQ ID Nos 203-206.

26. The antibody or a fragment thereof of claim 23, wherein the humanized antibody comprises a heavy chain variable region selected from SEQ ID Nos 201-202, and a light chain variable region selected from SEQ ID Nos 203-206.

27. The antibody or a fragment thereof of claim 23, wherein the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207-208.

28. The antibody or a fragment thereof of claim 23, wherein the humanized antibody comprises a light chain full sequence selected from SEQ ID Nos 209-212.

29. The antibody or a fragment thereof of claim 23, wherein the humanized antibody comprises a heavy chain full sequence selected from SEQ ID Nos 207-208, and a light chain variable region selected from SEQ ID Nos 209-212.

30. A complex comprising the antibody or fragment of claim 1, wherein the complex comprises the polypeptide or antibody bound to IgE protein.